Platelet Function In Subjects Research Articles

Dose-dependent effects of anthocyanin supplementation on platelet function in subjects with dyslipidemia: A randomized clinical trial.

BackgroundDyslipidemia induces platelet hyperactivation and hyper-aggregation, which are linked to thrombosis. Anthocyanins could inhibit platelet function in vitro and in mice fed high-fat diets with their effects on platelet function in subjects with dyslipidemia remained unknown. This study aimed to investigate the effects of different doses of anthocyanins on platelet function in individuals with dyslipidemia.MethodsA double-blind, randomized, controlled trial was conducted. Ninety-three individuals who were initially diagnosed with dyslipidemia were randomly assigned to placebo or 40, 80, 160 or 320 mg/day anthocyanin groups. The supplementations were anthocyanin capsules (Medox, Norway). Platelet aggregation by light aggregometry of platelet-rich plasma, P-selectin, activated GPⅡbⅢa, reactive oxygen species (ROS), and mitochondrial membrane potential were tested at baseline, 6 weeks and 12 weeks.FindingsCompared to placebo group, anthocyanins at 80 mg/day for 12 weeks reduced collagen-induced platelet aggregation (-3.39±2.36%) and activated GPⅡbⅢa (-8.25±2.45%) (P < 0.05). Moreover, compared to placebo group, anthocyanins at 320 mg/day inhibited collagen-induced platelet aggregation (-7.05±2.38%), ADP-induced platelet aggregation (-7.14±2.00%), platelet ROS levels (-14.55±1.86%), and mitochondrial membrane potential (7.40±1.56%) (P < 0.05). There were dose-response relationships between anthocyanins and the attenuation of platelet aggregation, mitochondrial membrane potential and ROS levels (P for trend <0.05). Furthermore, significantly positive correlations were observed between changes in collagen-induced (r = 0.473) or ADP-induced (r = 0.551) platelet aggregation and ROS levels in subjects with dyslipidemia after the 12-week intervention (P < 0.05).InterpretationAnthocyanin supplementation dose-dependently attenuates platelet function, and 12-week supplementation with 80 mg/day or more of anthocyanins can reduce platelet function in individuals with dyslipidemia.

Effects of a 8-week treatment with monoclonal antibody anti-PCSK9 therapy on platelet function in subjects affected by familial hypercholesterolemia

Effects of a 8-week treatment with monoclonal antibody anti-PCSK9 therapy on platelet function in subjects affected by familial hypercholesterolemia

Fibrinolytic Activity and Platelet Function in Subjects with Obstructive Sleep Apnoea and a Patent Foramen Ovale: Is There an Option for Prevention of Ischaemic Stroke?

Obstructive sleep apnoea (OSA) carries an increased risk of ischaemic stroke, but the underlying mechanism is not clear. As right-to-left shunting can occur through a patent foramen ovale (PFO) during periods of apnoea, we investigated nocturnal changes in fibrinolytic activity and platelet function in subjects who had OSA with or without PFO and in controls. We determined plasminogen activator inhibitor 1 (PAI-1) activity and antigen and platelet activation parameters. The severity of OSA was verified by polygraphy and PFO was detected by ear oximetry. We found a higher PAI-1 activity and antigen and a lower ratio of 2,3-dinor-PGF1α to 2,3-dinor-TXB2 in the subjects with OSA than in the controls. Linear regression analysis showed the apnoea-hypopnoea index (β-coefficient, 0.499; P = 0.032) and PFO (β-coefficient, 0.594; P = 0.015) to be associated independently with PAI-1 activity in the morning, while the increment in PAI-1:Ag from evening to morning was significantly associated with the presence of PFO (rs = 0.563, P = 0.002). Both OSA and PFO reduce fibrinolytic activity during nocturnal sleep. We hypothesize that subjects having both OSA and PFO may develop a more severe prothrombotic state during sleep than those having either OSA or PFO alone.

A Phase 1 Study of Prasugrel in Subjects with Sickle Cell Disease: Impact on Ex Vivo Platelet Reactivity

Abstract 1053 Introduction:There is evidence of increased platelet reactivity in subjects with sickle cell disease (SCD). This could contribute to vaso-occlusive complications that characterize the disease; thus, antiplatelet therapy may be useful in the management of SCD. Prasugrel, a novel thienopyridine P2Y12 ADP receptor antagonist, is an effective inhibitor of ADP-mediated platelet activation and aggregation, but it has not been evaluated in SCD. The present study examined 1) the utility of various platelet assays used to assess platelet reactivity in blood from subjects with SCD; and 2) the impact of prasugrel on platelet reactivity in subjects with SCD compared to healthy controls. Methods:Twenty-six adult subjects were enrolled and 25 completed the study: 12 with SCD and 13 well-matched healthy controls. Subjects were examined before and after 12±2 days of treatment with oral prasugrel (5.0 mg/day for subjects weighing <60 kg and 7.5 mg/day for subjects weighing ≥60 kg). Platelet reactivity to ADP at baseline and after 12 days of prasugrel treatment was assessed by 1) maximum platelet aggregation (MPA) to 5mM ADP using light transmission aggregometry (LTA); 2) area under the aggregation curve (AU.min) to 6.5 mM ADP using impedance aggregometry (IA); 3) P2Y12 reactivity units (PRU) by VerifyNow P2Y12 (VN); and 4) platelet reactivity index (PRI) by vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Baseline population differences and the within-group changes from baseline were analyzed using t-tests. The population differences for change from baseline were analyzed using an analysis of covariance model, with dose, subject group, and dose-by-subject group interaction as fixed effects, and baseline measurement as the covariate. Results:All data are shown as mean±SD. At baseline and prior to initiation of prasugrel, subjects with SCD showed increased platelet reactivity vs. healthy controls, as evidenced by VN (PRU: 407.9±39.6 vs. 322.5±74.2, p=0.003) and IA (AU.min: 106.4±27.9 vs. 76.5±13.2, p=0.002). However, there was no difference between subjects with SCD and healthy controls in baseline platelet reactivity with LTA (MPA: 73.1±14.4% vs. 80.4±23.2%, p=0.376). Baseline PRI by VASP was significantly lower in subjects with SCD than in healthy controls (PRI: 59.4±23.3% vs. 78.9±10.0%, p=0.018) (Figure).After 12 days of treatment with prasugrel, all measures of platelet reactivity were significantly reduced compared with baseline in both SCD subjects and healthy controls (p< 0.05 for each assay); absolute change from baseline were as follows: LTA (−33.4 vs. −49.9), IA (−63.2 vs. −49.5), VN (−197.4 vs. −212.0), and VASP (−46.0 vs. −49.9; all SCD vs. control respectively, Figure). Changes from baseline in subjects with SCD compared to changes from baseline in healthy controls were not statistically significant after adjusting for baseline.Prasugrel was safe and well tolerated with no serious adverse events observed during the study. No subject discontinued the study due to an adverse event (AE) and the majority of AEs were mild. No subjects with SCD reported any bleeding-related AEs. Conclusion:At baseline, compared with healthy controls, subjects with SCD had increased platelet aggregation to ADP in whole blood by two independent assays (VN and IA), but similar aggregation in platelet-rich plasma (LTA). These results may be influenced by the lower hematocrit and higher platelet count in subjects with SCD. At baseline, subjects with SCD had more variable VASP PRI values resulting in reduced mean PRI. It remains to be determined whether this is a reflection of altered ADP and/or PGE1 signaling in certain individuals with SCD. Prasugrel administration significantly attenuated ADP-stimulated platelet reactivity in SCD subjects as measured by LTA, IA, VN, and VASP. The extent of prasugrel inhibition of platelet function in SCD was similar to that observed in prasugrel-treated healthy controls as measured by all 4 assays. The present results demonstrate that prasugrel inhibits platelet function in subjects with SCD, and that this inhibition can be monitored by a variety of assays. These results provide the basis for future studies evaluating prasugrel for the treatment of vascular complications associated with SCD. [Display omitted] p value: change from baseline; error bars: arithmetic mean±SD for combined dose data Disclosures:Jakubowski:Eli Lilly and Company: Employment, Equity Ownership. Off Label Use: This abstract discusses prasugrel treatment in patients with sickle cell disease. Please see USPI for most up-to-date information. Zhou:Eli Lilly and Company: Employment, Equity Ownership. Small:Eli Lilly and Company: Employment, Equity Ownership. Winters:Eli Lilly and Company: Employment, Equity Ownership. Lachno:Eli Lilly and Company: Employment, Equity Ownership. Frelinger:Takeda: Research Funding; GLSynthesis: Research Funding; Daiichi Sankyo Company, Ltd. and Eli Lilly and Company: Consultancy, Research Funding. Howard:Daiichi Sankyo Company, Ltd. and Eli Lilly and Company: Research Funding. Payne:Eli Lilly and Company: Employment, Equity Ownership.

Haemorheological, endothelial and platelet function in subjects with hypertension: relationship to cardiovascular risk and influence of antihypertensive treatment.

Haemorheological, endothelial and platelet function in subjects with hypertension: relationship to cardiovascular risk and influence of antihypertensive treatment