Platelet-monocyte cross talk and tissue factor expression in stable angina vs. unstable angina/non ST-elevation myocardial infarction

Tissue factor (TF), the major procoagulant in vivo, is usually absent from blood cells. However, since both monocyte TF (MoTF) expression and platelet activation are present in acute coronary syndrome we hypothesized that MoTF expression may in part depend on monocyte platelet aggregate (MPA) formation in coronary artery disease (CAD). Patients with unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI, n?=?20) had significantly higher levels of MoTF (17.4?±?3.1MFI) and MPAs (CD42b:273?±?183MFI; CD62P:256.3?±?48.5MFI) than patients with stable angina (SA, n?=?40; MoTF:13.2?±?2.2MFI, p?=?0.001; CD42b:160?±?113MFI, p?=?0.025; CD62P:118.7?±?24.5MFI, p?=?0.018) as measured by whole blood flow cytometry on CD14+-cells. TF-activity of isolated mononuclear cells (MNC) was elevated in UA/NSTEMI (75?±?27?pg/mL) in comparison to SA (47?±?17?pg/mL, p?=?0.001) as determined by chromogenic assay, and TF mRNA expression in isolated MNC was more frequent in UA/NSTEMI than in SA (50% vs. 18.2%; p?=?0.017). MoTF expression significantly correlated with the constitutive platelet marker CD42b (r?=?0.69, p?相似文献   

Increased platelet reactivity in unstable angina patients is not related to C-reactive protein levels

Platelets are a major component of thrombi, and coronary thrombosis plays a key role in the pathogenesis of unstable angina (UA). Whether platelet aggregability is increased in UA patients however, is not known. Furthermore, no study has investigated the relationship between platelet reactivity and inflammation in UA patients In this study, venous blood samples were collected at admission in coronary care unit in 37 patients with unstable angina (Braunwald class IIIB) and in 37 sex- and age-matched patients with chronic stable angina (CSA). Patients taking thienopyridine or anticoagulant drugs were excluded from the study, as also were excluded patients with a history of acute myocardial infarction in the previous 12 months. Platelet aggregability was measured on flowing blood as time to occlude a ring coated with collagen-adenosine diphosphate (ADP), using the platelet function analyzer (PFA-100) system. By this method, the time to occlusion (closure time) is taken as a measure of platelet adhesion/aggregability, with shorter times indicating greater platelet reactivity.There were 23 men and 14 women in both groups, and age was 67.7?±?8 and 67.5?±?8 years in UA and SA, respectively (P?=?0.93). Closure time was significantly reduced in UA patients (78.8?±?14?s), compared to SA patients (93.3?±?19?s,?P?<?0.001). Among UA patients, serum C-reactive protein (CRP) levels had a median value of 5.1?mg/l (bottom and top quartile levels, 1.50–7.95). There was no significant correlation between closure time and CRP levels (r?=?0.22,?P?=?0.29). Our data show that, in patients with unstable angina there is an increase of platelet reactivity in response to ADP/collagen stimulation, which is not related to inflammation.     

The value of flow cytometry in the measurement of platelet activation and aggregation in human immunodeficiency virus infection

Human immunodeficiency deficiency virus (HIV) infection is associated with chronic inflammation and an increased risk of thrombotic events. Activated platelets (PLTs) play an important role in both thrombosis and inflammation, and HIV has been shown to induce PLT activation by both direct and indirect mechanisms. P-selectin (CD62P) is a well-described marker of PLT activation, and PLT glycoprotein (GP) IV (CD36) has been identified as a marker of PLT aggregation. Data on PLT function in the context of HIV infection remain inconclusive. Laboratory techniques, such as flow cytometry, enable the assessment of PLTs in their physiological state and environment, with minimal artifactual in vitro activation and aggregation. In this study, we describe a novel flow cytometry PLT assay, which enabled the measurement of PLT function in HIV infection. Forty-one antiretroviral-naïve HIV-positive individuals and 41 HIV-negative controls were recruited from a clinic in the Western Cape. Platelet function was evaluated by assessing the response of platelets to adenosine diphosphate (ADP) at two concentrations (0.04?mM, 0.2?mM). The percentage expression and mean fluorescence intensity (MFI) of CD62P and CD36 was used to evaluate platelet function. These were then correlated with platelet (PLT) count; CD4 count; % CD38/8; viral load and D-dimers. The % CD62P levels were higher in HIV-positive patients (HIV % CD62P 11.33[5.96–29.36] vs. control 2.48[1.56–6.04]; p?<?0.0001). In addition, the HIV group showed higher CD62P MFI levels (HIV CD62P MFI 3.25?±?7.23 vs. control 2.35?±?1.31, p?=?0.0292). Baseline levels of %CD36 expression were significantly higher in HIV-positive patients (%CD36 12.41[6.31–21.83] vs. control 6.04[1.34–13.15]; p?=?0.0091). However, the baseline CD36MFI showed no significant difference between the two groups (HIV CD36 MFI 3.09?±?0.64 vs. control 2.44?±?0.11, p?=?0.4591). The HIV group showed higher levels of % CD36 expression post stimulation with 0.04?mM ADP 43.32?±?27.41 vs. control 27.47?±?12.95; p?<?0.0214) and no significant difference at 0.2?mM ADP (HIV % CD36 39.06?±?17.91 vs. control 44.61?±?18.76; p?=?0.3277). Furthermore, the HIV group showed a single phase response to ADP as compared to the control group, which showed a normal biphasic response. We concluded that PLT flow cytometry is valuable in the assessment of levels of PLT activation, and further, that the addition of an endogenous agonist, such as ADP, enabled the measurement of PLT function in HIV infection. We were able to show that, although PLTs are significantly activated in HIV compared to uninfected controls, they retain their functional capacity.     

Increased soluble glycoprotein V concentration during the acute onset of unstable angina pectoris in association with chronic cigarette smoking

Platelet hyperactivity is important in the pathobiology of acute coronary syndromes. Glycoprotein V (GPV) is an integral membrane protein of platelets in the function of the GPIb-V-IX receptor for vWf/shear-dependent platelet adhesion in arteries. Soluble GPV is a novel marker of platelet activation. The aim of this study is to assess circulating soluble GPV levels in unstable angina pectoris (UA). Twenty-one patients (15 men, six women, aged 52?±?7 years) with UA pectoris were studied. The inclusion criteria were angina at rest lasting >20?min during the preceding 6?h, with transient ST segment depression and/or T wave inversion and no evidence of myocardial infarction detected with the use of cardiac troponin-T. Coronary artery stenosis was angiographically confirmed in all patients. Twenty age- and sex-matched healthy adults (14 men, six women, aged 48?±?7 years) served as controls. There were no significant differences among the studied groups with respect to age, sex, obesity, smoking, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride and platelet counts. Plasma-soluble GPV concentrations were higher in the UA patient group (126?±?46?ng/ml) than those in the healthy controls (82?±?15?ng/ml) (P?=?0.001). There was a significant correlation only between plasma-soluble GPV levels and smoking (r?=?0.526, P?=?0.0001). Smoker UA patients had higher levels of soluble GPV than the non-smoker patients (139?±?40 vs. 113?±?50?ng/ml, respectively, P?=?0.02). However, soluble GPV levels were similar in smoker and non-smoker healthy controls (P?=?0.2). It is concluded that soluble GPV concentrations are significantly increased during the acute clinical course of unstable angina pectoris, indicating that soluble GPV may be useful marker of platelet activation in those patients. The level of the molecule is significantly affected from smoking in those patients.     

Platelet bound oxLDL shows an inverse correlation with plasma anaphylatoxin C5a in patients with coronary artery disease

Both oxidized lipids as well as the complement system contribute to atherothrombosis. The expression of complement receptors correlates with the expression of platelet activation markers, and platelet bound oxidized low-density lipoprotein (oxLDL) modulates platelet function. In the present study, we investigated the relationship of markers of complement activation, the anaphylatoxins C5a and C3a, and oxidized low-density lipoprotein.

Two hundred and seven patients with coronary artery disease (CAD) were analyzed in this study. Using enzyme-linked immunosorbent assays, plasma levels of oxLDL, C3a, and C5a were measured. Moreover, we assessed platelet bound oxLDL by flow cytometry. The overall level of C5a in the troponin negative group (stable angina (SA) and unstable angina (UA)) compared to the troponin positive group (non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI)) did not differ significantly (62.7 ± 32.4 ng/ml versus 65.8 ± 40.3 ng/ml). While C5a and C3a showed a significant correlation with each other (r = 0.25, p < 0.001), there was no statistically significant relationship between C3a and platelet bound oxLDL (r = 0.06, p = 0.37). Furthermore, plasma oxLDL did not correlate with either C3a or C5a. However, we observed a moderate, yet significant negative correlation between plasma C5a and platelet bound oxLDL (r = ?0.15, p = 0.04). Partial correlation analysis correcting for the presence of acute coronary syndrome (ACS), troponin status or the subgroups SA, UA, NSTEMI, or STEMI did not alter this correlation substantially. Interestingly, flow cytometric analysis of human platelets showed increased expression of C5aR and P-selectin after in vitro stimulation with oxLDL.

In conclusion, the complement anaphylatoxin C5a shows an inverse correlation with platelet bound oxLDL. The relationship of oxidized lipids to particular complement components may add to the platelet–lipid interplay in atherogenesis and trigger future clinical and mechanistic studies.     

Intracoronary β‐irradiation enhances balloon‐injury‐induced tissue factor expression in the porcine injury model

Intracoronary brachytherapy (ICBT) effectively reduces restenosis but is associated with late thrombosis. Since tissue factor (TF) is an important mediator of arterial thrombosis, we tested the hypothesis that ICBT results in persistently augmented TF expression. Coronary arteries from 12 pigs were randomized to: control (C; no injury), oversized balloon injury (BI), or BI followed by ICBT. Animals were sacrificed at 1, 7, 14, or 60 days postprocedure, and coronary arteries collected for expression analyses and immunostaining. ICBT‐treated arteries had higher TF antigen and activity at all time‐points compared to BI arteries (Western blot: 16?571?± 2090 vs 10?135?±?2939 densitometric units, p?=?0.001; ELISA: 0.42?±?0.13?nM vs 0.25?±?0.14?nM, p?=?0.001; TF activity assay: 0.303?±?0.11?nM vs 0.18?± 0.07?nM, p?=?0.01; immunohistochemical staining: 30.6?±?6.6% vs 11.5%?±?3.2%, p?=?0.01). TF expression increased following BI, increased further following ICBT, and persisted for the duration of the study. We conclude that TF expression increases after BI, but is further increased and persists for a longer duration following ICBT, suggesting that a TF‐mediated mechanism may play a role in late thrombosis following ICBT. (Int J Cardiovasc Intervent 2004; 1:?20–27)     

Plasma levels of soluble glycoprotein VI (sGPVI) are associated with ischemic stroke

Platelet collagen receptor glycoprotein VI (pGPVI) is elevated in patients with acute coronary syndrome (ACS) and ischemic stroke. Recently, we developed a novel bead-based sandwich immunoassay to determine soluble GPVI (sGPVI), which has been validated in ACS patients. This study aimed to evaluate the plasma levels of sGPVI and pGPVI expression in patients with suspected stroke. We consecutively evaluated 176 patients, who were admitted to the stroke unit. Surface expression of pGPVI was determined by flow cytometry, sGPVI concentrations were determined using our sandwich immunoassay. Unlike patients with TIA, patients with stroke showed significantly decreased plasma levels of sGPVI compared to patients with non-ischemic (NI) events (TIA: mean [µg/L]?±?standard deviation): 6.1?±?2.1 vs. NI: 8?±?4; p?=?0.192; stroke: 5.9?±?2.3 vs. NI; p?=?0.013), whereas for pGPVI, patients with TIA and ischemic stroke revealed a significantly increased platelet surface expression compared to NI patients (TIA: mean fluorescence intensity [MFI]?±?standard deviation): 20.9?±?5.4 vs. NI: 17.6?±?5.2; p?=?0.021; stroke: 20.3?±?6.2 vs. NI; p?=?0.016). Using logistic regression analysis, both sGPVI (p?=?0.002) and pGPVI (p?=?0.012) are independently associated with ischemic stroke compared to other laboratory markers. To predict the individual risk for ischemic stroke using the plasma levels of sGPVI, receiver operating characteristic (ROC) analysis determined an optimal cutoff value of sGPVI at 6.5?µg/l, thus, patients with decreased plasma levels (<6.5?µg/l) have a 1.5-fold adjusted odds ratio (95%confidence interval, 1.4–2.7). Lower plasma levels of sGPVI are associated with the slightly elevated risk of stroke and may be a promising novel biomarker.     

Correlation of TSLP,IL-33, and CD4 + CD25 + FOXP3 + T regulatory (Treg) in pediatric asthma

Objective: Newly discovered cytokines TSLP and IL33 are being studied as important indicators of Th2 inflammation and their effect on Treg cells is likely to modulate immune response. We attempted to study TSLP and IL-33 and then correlated with Tregs in order to find possible biomarker in these patients. Methods: Sixty-five children (37 with asthma only and 28 with asthma and rhinitis) aged 6.4?±?3.2 years (patient group) and 15 healthy children aged 8.0?±?2.6 years (control group) were recruited in this study. In vitro analysis of TSLP and IL-33 was done in serum samples of 65 newly diagnosed children for allergic asthma and 15 healthy children using the sandwich ELISA method. The expression of Treg cells (CD4?+?CD25?+?FOXP3+) was analyzed by flow cytometry. Results: The mean TSLP in the patient group (592?±?68?pg/ml) was significantly higher than controls (215?±?45?pg/ml) (p?<?0.05). Alternatively, the expression of FOXP3?+?T reg cells was significantly lower in the patient group (52?±?36) compared with the controls (95.9?±?3.6) (p?=?0.003). IL-33 was also significantly higher (4044?±?413?pg/ml) in the patient group compared with the controls (3282?±?331.5?pg/ml) (p?=?0.0001). The expression of Treg cells was negatively correlated with the TSLP (r?=??0.23, p?=?0.07). Asthma control test (ACT) was also negatively correlated with TSLP in the patient group (r?=??0.14, p?>?0.05). Conclusion: Children with asthma show elevated serum levels of TSLP, which correlated negatively with asthma control test and Treg cells. TSLP may be used as a biomarker for inflammation in pediatric asthma patients.     

Relationship between placental grade and mean platelet volume

Abstract

This study was performed to investigate the correlation between mean platelet volume, as an indicator of thrombocyte function, and placental grade classified by the Grannum scoring system. Placental sonographic images were graded according to the Grannum scoring system, and synchronous haemogram samples were taken from patients who attended foetal assessments during the second and third trimesters. A total of 75 patients were in their second trimester, and 40 patients were in their third trimester. The relation between week of pregnancy and placental Grannum score was significant (p?<?0.001); i.e. placental Grannum score increased with gestational age. The association between Grannum score and mean platelet volume was analysed, including trimester and mean platelet volume, by linear regression analysis. The results indicated a distinct trimester-independent correlation between mean platelet volume and Grannum score (partial correlation coefficient?=?0.455; p?<?0.001). However, no correlation was observed between Grannum score and gravity (r?=?0.87; p?=?0.356), parity (r?=?0.97; p?=?0.302) or abortion (r?=?0.011; p?=?0.91). The correlation between mean platelet volume and placental calcification was investigated, and mean platelet volume in patients with a calcified placenta was 8.23?±?1.14, whereas mean platelet volume in placentas with no calcification was 7.92?±?1.18 (p?=?0.233). Mean platelet volume was an independent indicator of Grannum score, which is an indicator of placental grade, in women in the second and third trimester of pregnancy. Assessing mean platelet volume during routine screening may identify functional placental disorders.     

The effect of weight loss on the mean platelet volume in obese patients

Obesity is a chronic metabolic disorder associated with cardiovascular disease and atherosclerosis. Platelet activation and aggregation are central processes in the pathophysiology of cardiovascular disease. Mean platelet volume (MPV), a determinant of platelet activation, is a newly emerging risk marker for atherothrombosis. Our objective was to evaluate the effect of weight loss on the MPV in obese patients. We selected 30 obese women patients and 30 non-obese healthy women subjects. All obese patients took the same content and caloric diet treatment for 3 months. Body mass index (BMI), metabolic parameters and MPV were measured at baseline and after 3 months diet treatment. Before diet treatment, obese group had significantly higher MPV levels than in the non-obese control group (8.18?±?1.09 fl vs. 8.01?±?0.95 fl, p?=?0.004). MPV showed positive correlations with BMI level in the obese group (r?=?0.43, p?=?0.017). BMI significantly decreased after diet treatment (36.2?±?3.2?kg/m² vs. 34.7?±?3.6?kg/m², p?<?0.001), in the obese group. MPV significantly decreased after diet treatment in the obese group (8.18?±?1.09 fl vs. 8.08?±?1.02 fl, p?=?0.013). There was a positive correlation between weight loss and reduction in MPV (r?=?0.41, p?=?0.024). In addition to its well-known positive effects on cardiovascular disease risk, weight loss may also possess significant anti-platelet activation properties that can contribute its antiatherogenic effects in obese patients.     

Measurement of red blood cell 6-thioguanine nucleotide is beneficial in azathioprine maintenance therapy of Chinese Crohn’s disease patients

Objective: It remains controversial whether 6-thioguanine nucleotide (6-TGN)-based dose adjusting can be beneficial in azathioprine (AZA) therapy. This study is designed to assess the role of 6-TGN concentrations in maintaining clinical remission in Chinese patients with Crohn’s disease (CD).

Material and method: We performed a prospective observational study and collected data of CD patients in the First Affiliated Hospital of Anhui Medical University from June 2013 to April 2014. Demographic material, CD activity index, 6-TGN concentration, and laboratory tests were recorded at baseline and at each visit. In addition, 6-TGN was measured when drug adverse effects occurred. All patients achieved maintenance stage were administered a stable AZA dose at least 3 months before enrollment and were followed up at least 12 months. Thiopurine S-methyltransferase (TPMT) genotype was measured before AZA treatment.

Results: Sixty-nine patients receiving maintenance therapy were analyzed. A positive correlation was found between 6-TGN levels and AZA dose (r?=?0.258, p?=?0.032). The mean 6-TGN concentration was 302.06?±?115.84 in the remission group vs. 264.94?±?164.53?pmol/8?×?10⁸ RBC in those with active disease (t?=?0.847, p?=?0.40), and 197.74?±?66.54?pmol/8?×?10⁸ RBC in patients who relapsed vs. 310.26?±?122.38?pmol/8?×?10⁸ RBC for those in sustained remission (t=??2.541, p?=?0.013). In the leukopenia group, the 6-TGN concentration was 469.11?±?115.53?pmol/8?×?10⁸ RBC vs. 257.31?±?83.74?pmol/8?×?10⁸ RBC in the non-leukopenia group (t?=?7.622, p?r=??0.326, p?=?0.006).

Conclusions: 6-TGN measurement is a helpful method of preventing disease relapse and avoiding leukopenia in individual azathioprine maintenance therapy.     

Association of platelet activation markers with recurrence of atrial fibrillation after pulmonary vein isolation

Atrial fibrillation (AF) is known to cause platelet activation. AF and its degree of thrombogenesis could be associated with monocyte-platelet aggregates (MPAs). We investigated on whether the content of MPAs or other platelet activation markers is associated with the recurrence of AF after pulmonary vein isolation (PVI). A total of 73 patients with symptomatic AF underwent PVI. After 6 months, all patients were evaluated for episodes of AF recurrence. At the same time, flow-cytometric quantification analyses were performed to determine the content of MPAs. Further platelet activation parameters were detected by using either cytometric bead arrays or quantitative immunological determination. Patients with recurrent AF (n = 20) compared to individuals without AF relapse (n = 53) were associated with an increased content of MPAs (43 ± 3% vs. 33 ± 2%, p = 0.004), as well as an increased CD41 expression on monocytes (191 ± 20 vs. 113 ± 6, p = 0.001). The level of the soluble platelet activation markers such as D-dimer, sCD40L, and sP-selectin did not differ between these groups. The content of MPAs correlated weakly with the level of sCD40L (r = 0.26, p = 0.03), but not with sP-selectin and D-dimer, whereas sP-selectin and sCD40L correlated with each other (r = 0.38, p = 0.001). Only the cellular marker of platelet activation, the content of MPAs, was increased in patients with recurrent AF after PVI. In contrast, soluble markers remained unaltered. These data indicate a distinct mechanism and level of platelet activation in AF. The clinical relevance of MPAs in identifying AF recurrence or in guiding the therapy with anticoagulants remains to be elucidated.     

Cystatin C is better than albuminuria as a predictor of pulse wave velocity in hypertensive patients

Introduction: Arterial stiffness is important in the evaluation of the cardiovascular risk in both general population and hypertensive patients. In this study, we aimed to investigate the associations of both serum cystatin C levels and albuminuria with arterial stiffness in healthy controls and hypertensive patients.

Patients and methods: Seventy-six healthy controls (male/female?=?44/32) and 76 hypertensive patients (male/female?=?43/33) were enrolled. Arterial stiffness parameters such as augmentation index (AIx) and pulse wave velocity (PWV) were non-invasively measured with the Arteriograph (Tensiomed Ltd., Budapest, Hungary).

Results: AIx (31.92?±?14.31 vs. 27.95?±?11.03, p?=?0.03) and PWV (9.84?±?1.62 vs. 8.87?±?2.04, p?p?=?0.002) and higher serum cystatin C levels [0.76 (0.67–0.95) vs. 0.68 (0.62–0.78) mg/L, p?=?0.03]. In the hypertensive group, AIx was significantly correlated with PWV (r?=?0.519, p?r?=?–0.438, p?=?0.003), mean arterial pressure (MAP) (r?=?0.288, p?=?0.015) and urinary albumin–creatinine ratio (ACR) (r?=?0.386, p?=?0.004). PWV was associated with serum cystatin C (r?=?0.442, p?=?0.003) and MAP (r?=?0.377, p?=?0.001). In the linear regression analysis (model r?=?0.577, p?=?0.006) for the prediction of PWV in hypertensive patients, MAP, urinary ACR, age and serum cystatin C levels were included as independent variables. Cystatin C was found to be the significant determinant of PWV in hypertensive patients.

Conclusion: Multivariate analysis revealed that serum cystatin C but not albuminuria was significantly associated with PWV in hypertensive patients. Serum cystatin C may be better than albuminuria as a predictor of arterial stiffness in hypertensive patients.     

Circulating platelet and neutrophil activation correlates with the clinical course of unstable angina

Recent studies have suggested important roles of inflammation in the pathophysiology of unstable angina (UA). We investigated whether activation of the circulating platelets and neutrophils were implicated in inflammatory reactions associated with unstable angina Expressions of platelet P-selectin and neutrophil CD11b, and neutrophil–platelet aggregates were evaluated by flow cytometry in anticoagulated peripheral venous blood from 71 patients with UA and 22 patients with stable angina (SA). Expressions of platelet P-selectin and neutrophil CD11b, and neutrophil–platelet aggregates on the admission day were all significantly higher in 71 patients with UA than 22 with SA (median, mean fluorescence intensity [MFI]: 7.00 vs 4.51, P < 0.01, 64.68 vs 47.75, P = 0.0007; and % of 10 000 neutrophils: 7.84 vs 3.40, P = 0.0001, respectively). These three parameters in 43 patients with UA were significantly decreased (MFI: 4.23, P = 0.003, 50.82, P = 0.0003; and % of 10 000 neutrophils: 5.04, P = 0.0001, respectively) 7 days after the first measurement. These results indicate that circulating activated platelets and neutrophils are more strongly implicated in the acute phase of UA. These findings also suggest that thrombus formation after rupture of atherosclerotic plaques as well as plaque formation involves inflammatory reactions.     

Serum uric acid is associated with non-dipping circadian pattern in young patients (30–40 years old) with newly diagnosed essential hypertension

Background: We aimed at evaluating the relationship between the circadian blood pressure rhythm and UA level in young patients (30–40 years old) with newly diagnosed essential hypertension. Methods: The study included 62 essential hypertensive patients and 29 healthy controls (20 men, 35?±?3 years) divided into two groups according to 24-hour ABPM resuts: 30 dippers and 32 nondippers. Results: Nondippers showed significantly higher both serum UA levels compared to dippers and controls (6.1?±?0.7, 5.2?±?0.9 and 4.1?±?0.9?mg/dL, p?<?0.001, respectively); and high sensitivity C-reactive protein (hsCRP) (4.1?±?2.2?mg/L, 3.3?±?1.9?mg/L, and 1.4?±?0.9?mg/L, p?<?0.001, respectively). After adjusting for age, sex, body mass index, smoking, creatinine levels, hsCRP and comorbidity, multivariate logistic regression analysis revealed an independent association between serum UA levels and nondipper pattern (OR 2.44, 95%CIs 1.4–4.1, p?=?0.002). Conclusion: Serum UA is independently associated with nondipper circadian pattern in young patients with newly diagnosed essential hypertension.     

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.     

The Retention Index Test Homburg (RTH-II): Response to clopidogrel and comparison with aggregometry and CD62P-expression

The Retention Index Test Homburg (RTH-II) is quoted to detect effects of shear stress on platelets, which involve ADP receptor signaling. RTH-II might be a tool for monitoring antiplatelet therapy for compounds that interfere with ADP induced platelet activation and secretion. In a series of investigations, we used an ADP (2?µM) triggered RTH-II in parallel with light-transmittance aggregometry and flow cytometry in subjects before and after clopidogrel. A loading dose of 225?mg clopidogrel leads to a significant reduction (p?<?0.01) in the ADP-stimulated retention index (RI) from 69?±?15 to 48?±?21%, in the aggregation response to 5?µM ADP (from 50?±?20 to 29?±?21%) and the expression of CD62P (from 64?±?11 to 41?±?17%). Correlation analysis showed that the RI corresponds significantly to CD62P-expression (p?<?0.01) but not to aggregation. We also found a strong correlation (p?<?0.01) between the ADP-stimulated RI and the expression of CD62P after stimulation with 2?µM ADP, whereas no correlation was seen for RI vs. binding of PAC-1 or aggregation. Platelets not retained in the filter had lower CD62P expression than measured in the sample before the filter passage (54 vs. 35%). A direct interaction of CD62P with platelet ligands might lead to enhanced retention in RTH and explain the correlation of RI with CD62P expression. The RTH-II might be a simple and easy to handle platelet function assay for monitoring effects on P2Y₁₂-inhibitors on platelet degranulation, perhaps in addition to aggregometry.     

Anxiety disorders are associated with increased plasma adrenomedullin level and left ventricular hypertrophy in patients with hypertension

Objective: To investigate the association between anxiety disorders and left ventricular hypertrophy in patients with essential hypertension.

Methods: Left ventricular structure and function were assessed with echocardiography in 56 patients with essential hypertension and anxiety disorder (study group) and in 56 patients with hypertension only (control group). Serum adrenomedullin levels were also measured in these patients.

Results: There was no statistically significant difference in the left ventricular ejection fraction between the study and the control group (54.21?±?88.81% versus 56.01?±?7.85%, p?>?0.05). The left ventricular mass index (LVMI) in study group was higher than in control group (137.05?±?9.42 versus 123.57?±?7.01?g/m², p?=?0.001). The plasma levels of adrenomedullin in study group was higher than in control group (25.97?±?5.48 versus 18.32?±?6.97?ng/L, p?=?0.001). Levels of plasma adrenomedullin were positively correlated with LVMI in the study (r?=?0.734, p?r?=?0.592, p?Conclusion: Anxiety disorders are associated with elevated plasma adrenomedullin levels and increased left ventricular hypertrophy in patients with essential hypertension. The clinical significance of these changes requires further investigation.     

Upregulation of CD40/CD40L system in rheumatic mitral stenosis with or without atrial fibrillation

Thrombelastography (TEG) analyses the status of blood coagulation including abnormalities associated with low platelet count. The aim of this study was to investigate the changes in TEG parameters in idiopathic thrombocytopenic purpura (ITP) patients. Thirty nine patients with ITP (platelet count?<?100?×?103 µl^?1) were included in the study. Age-matched 17 patients with thrombocytopenia due to chemotherapy were selected as a control group. Platelet count was positively correlated with maximum clot formation (MCF) in INTEM (r?=?0.716, p?<?0.001) and MCF in EXTEM (r?=?0.679, p?<?0.001); negatively correlated with clot formation time (CFT) in INTEM (r?=??0.755, p?<?0.001) and CFT in EXTEM (r?=??0.585, p?<?0.001) in ITP patients. Platelet count was positively correlated with MCF in INTEM (r?=?0.776, p?<?0.001) and MCF in EXTEM (r?=?0.878, p?<?0.001); negatively correlated with CFT in INTEM (r?=??0.627, p?<?0.001) in control group. Receiver operating characteristic curves to describe the critical platelet count and fibrinogen level that affect MCF revealed 31?×?103?µl^?1 and 375 mg?dl^?1 as cut-off values, respectively. In conclusion, ROTEM determines the contribution of fibrinogen and platelets to clot strength in patients with ITP. MCF appears to be the most important TEG parameter in predicting bleeding in ITP patients that makes TEG superior to other hemostatic tests.     

Monocytes circulate in constant reversible interaction with platelets in a [Ca2+]-dependent manner

Abstract

We aimed to provide evidence that blood monocytes belonging to all subsets predominantly circulate in constant and usually reversible interactions with platelets, which are predominantly [Ca2+] dependent. The proportions of monocyte–platelet aggregates (MPAs) attributable to individual monocyte subsets in fresh and promptly processed heparin-anticoagulated blood from 10 healthy subjects (median age 35 years, 50% male) were analysed by flow cytometry and compared to samples anticoagulated with a potent [Ca2+] chelator, ethylenediaminetetraacetic acid (EDTA). Additional experiments with [Ca2+] depletion or supplementation were also performed. Monocytes subsets were defined as CD14++CD16–CCR2+ cells (Mon1), CD14++CD16+CCR2+ cells (Mon2) and CD14+CD16++CCR2? cells (Mon3). Vast majority of monocytes showed aggregation with platelets in heparinised samples, but most monocytes were free of platelets when EDTA was used (p?p?=?0.005 for all subsets). Supplementation with CaCl₂ resulted in dose-dependent increase in MPAs (p?p?p?=?0.004). In healthy subjects monocytes circulate in constant, but predominantly reversible and [Ca2+]-dependent aggregation with platelets. These observations may reflect a complex involvement of platelets in regulation of monocyte activity.