An imbalance in coagulation is associated with cardiovascular events. For prevention and treatment, anticoagulants, currently mainly xabans and gatrans, are used. The purpose of the present study was to provide a head-to-head comparison since there are no studies directly evaluating these novel anticoagulants. An additional aim was to find whether selected anthropological and biochemical factors can affect their anticoagulant properties as they are used in fixed doses. In this cross-sectional study, blood from 50 generally healthy donors was collected, and coagulation responses to dabigatran, argatroban, rivaroxaban, and apixaban, at a concentration of 1 μM, were analyzed. Heparin was used as a positive control. Prothrombin time (PT) expressed as international normalized ratio (INR) and activated partial thromboplastin time (aPTT) were measured and compared. Rivaroxaban was the most active according to PT/INR while argatroban according to aPTT. The ex vivo anticoagulant effect measured by INR correlated inversely with body mass index (BMI) in all four anticoagulants tested. Shortening of aPTT was associated with higher cholesterol and triglyceride levels. No sex-related differences were observed in response to the anticoagulant treatments. As this was an ex vivo study and pharmacokinetic factors were not included, the influence of BMI is of high therapeutic importance.
- MeSH
- antikoagulancia * farmakologie MeSH
- arginin * analogy a deriváty MeSH
- dabigatran farmakologie MeSH
- dospělí MeSH
- hemokoagulace * účinky léků MeSH
- index tělesné hmotnosti MeSH
- INR MeSH
- kyseliny pipekolové * farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- parciální tromboplastinový čas MeSH
- protrombinový čas MeSH
- průřezové studie MeSH
- pyrazoly farmakologie MeSH
- pyridony farmakologie farmakokinetika MeSH
- rivaroxaban * farmakologie MeSH
- sulfonamidy farmakologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Platelet aggregation is a complicated process mediated by different signaling pathways. As the process is highly complex and apparently redundant, the relationships between these pathways are not yet fully known. The aim of this project was to study the interconnections among seven different aggregation pathways in a group of 53 generally healthy volunteers aged 20 to 66 years. Platelet aggregation was induced with thrombin receptor activating peptide 6 (TRAP), arachidonic acid (AA), platelet activating factor 16 (PAF), ADP, collagen, thromboxane A2 analogue U46619 or ristocetin (platelet agglutination) ex vivo in fasting blood samples according to standardized timetable protocol. Additionally, some samples were pre-treated with known clinically used antiplatelet drugs (vorapaxar, ticagrelor or acetylsalicylic acid (ASA)). Significant correlations among all used inducers were detected (Pearson correlation coefficients (rP): 0.3 to 0.85). Of all the triggers, AA showed to be the best predictor of the response to other inducers with rP ranging from 0.66 to 0.85. Interestingly, the antiplatelet response to ticagrelor strongly predicted the response to unrelated drug vorapaxar (rP = 0.71). Our results indicate that a response to one inducer can predict the response for other triggers or even to an antiplatelet drug. These data are useful for future testing but should be also confirmed in patients.
The process of platelet aggregation is often influenced by several factors including sex and age. A literature review confirmed the existence of sex-related differences in platelet aggregation. Although 68 out of 78 papers found such differences, there are still some controversies regarding these differences, which can be due to multiple factors (age, trigger, concomitant disease, sample handling, etc.). These outcomes are discussed in line with novel results obtained from a local study, in which blood samples from a total of 53 overall healthy women and men with ages ranging from 20 to 66 years were collected. Aggregation was induced with seven different triggers (ristocetin, thrombin receptor activating peptide 6 [TRAP-6], arachidonic acid [AA], platelet-activating factor 16 [PAF-16], ADP, collagen, or thromboxane A2 analog U-46619) ex vivo. In addition, three FDA-approved antiplatelet drugs (vorapaxar, ticagrelor, or acetylsalicylic acid [ASA]) were also tested. In general, women had higher aggregation responses to some agonists (ADP, TRAP), as well as lower benefit from inhibitors (ASA, vorapaxar). The aggregatory responses to AA and TRAP decreased with age in both sexes, while responses to ADP, U-46619, and PAF were affected by age only in women. In conclusion, more studies are needed to decipher the biological importance of sex-related differences in platelet aggregation in part to enable personalized antiplatelet treatment.
- MeSH
- adenosindifosfát farmakologie MeSH
- agregace trombocytů * MeSH
- Aspirin terapeutické užití MeSH
- inhibitory agregace trombocytů * terapeutické užití MeSH
- kyselina 15-hydroxy-11 alfa,9 alfa-(epoxymethano)prosta-5,13-dienová farmakologie MeSH
- kyselina arachidonová farmakologie MeSH
- laktony farmakologie MeSH
- lidé MeSH
- trombocyty MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
A polyphenol-rich diet has beneficial effects on cardiovascular health. However, dietary polyphenols generally have low bioavailability and reach low plasma concentrations. Small phenolic metabolites of these compounds formed by human microbiota are much more easily absorbable and could be responsible for this effect. One of these metabolites, 4-methylcatechol (4-MC), was suggested to be a potent anti-platelet compound. The effect of 4-MC was tested ex vivo in a group of 53 generally healthy donors using impedance blood aggregometry. The mechanism of action of this compound was also investigated by employing various aggregation inducers/inhibitors and a combination of aggregometry and enzyme linked immunosorbent assay (ELISA) methods. 4-MC was confirmed to be more potent than acetylsalicylic acid on both arachidonic acid and collagen-triggered platelet aggregation. Its clinically relevant effect was found even at a concentration of 10 μM. Mechanistic studies showed that 4-MC is able to block platelet aggregation caused by the stimulation of different pathways (receptors for the von Willebrand factor and platelet-activating factor, glycoprotein IIb/IIIa, protein kinase C, intracellular calcium elevation). The major mechanism was defined as interference with cyclooxygenase-thromboxane synthase coupling. This study confirmed the strong antiplatelet potential of 4-MC in a group of healthy donors and defined its mechanism of action.
- MeSH
- fenoly MeSH
- imunologické testy * MeSH
- katecholy * farmakologie MeSH
- lidé MeSH
- polyfenoly MeSH
- vyšetření funkce trombocytů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Background: Acupuncture has become a viable option for migraine prophylaxis in Europe; however, despite its wide use, more data on the short- and long-term cost-effectiveness are needed when considering the perspectives of a paying third-party, the patient, and of society in general. The aim was to evaluate the cost and effectiveness of adjuvant acupuncture to pharmacologic treatment vs pharmacologic treatment alone in migraine patients after a 3-month acupuncture course and a 6-month follow-up from all perspectives. Methods: The study involved an open-label randomized clinical trial of patients receiving acupuncture (n=42), and a waiting list control group (n=44). The number of migraine days during the last 28 days, as well as direct and indirect costs were considered. The trial was registered under DRKS00009803. Results: The total cost per patient reached €696 vs €285 after 3 months of acupuncture and €66 vs €132 in the acupuncture and control groups after a 6-month follow-up, respectively (P=0.071). The trends observed in effectiveness and costs from all perspectives are discussed. Conclusion: The inclusion of acupuncture in health care results beneficial mainly for its observed trend in reduced losses of productivity and income, with the latter often exceeding the costs of acupuncture treatment. As such, acupuncture may be recommended as an adjuvant treatment in migraine prophylaxis to standard pharmacotherapy.
- Publikační typ
- časopisecké články MeSH
Background: Adjuvant acupuncture for the symptomatic treatment of migraine reduces the frequency of headaches and may be at least similarly effective to treatment with prophylactic drugs. Methods: This article describes an open-label randomized controlled clinical trial with two groups: the intervention group (n=42) and the waiting-list control group (n=44). This study occurred at the Czech-Chinese Center for Traditional Chinese Medicine at the University Hospital Hradec Kralove between October 2015 and April 2017. Results: After 12 weeks of acupuncture, the number of migraine days was reduced by 5.5 and 2.0 days in the acupuncture and the waiting-list control groups, respectively, with a statistically significant inter-group difference of 2.0 migraine days (95% CI: -4 to -1). A significantly greater reduction in the number of migraine days per 4 weeks was reached at the end of the 6-month follow-up period in the acupuncture vs. control groups (Δ -4.0; 95% CI: -6 to -2). A statistically significant difference was observed in the number of responders to treatment (response defined as at least a 50% reduction in average monthly migraine day frequency) in the acupuncture vs waiting-list control groups (50% vs 27%; p<0.05) at the end of the intervention. A significantly greater percentage of responders to treatment was noted in the intervention vs control groups at the 6-month follow-up (81% vs 36%; p<0.001). Conclusion: Acupuncture can reduce symptoms and medication use, both short term and long term, as an adjuvant treatment in migraine prophylaxis in Czech patients.
- Publikační typ
- časopisecké články MeSH
