dinoprost and Thromboembolism

Enhanced oxidative stress occurs in atrial fibrillation (AF), however its impact on the efficacy and safety of anticoagulation is unknown. We sought to evaluate whether 8-isoprostaglandin F2 (8-isoprostane) levels are associated with clinical outcomes in anticoagulated AF patients.. In a study involving 243 AF patients (median age 69 years), we measured serum 8-isoprostane, along with prothrombotic markers, including plasma fibrin clot permeability, clot lysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor (VWF), and fibrinolytic proteins. Ischemic cerebrovascular events, major bleeding, and death were recorded during a median follow-up of 53 months while on anticoagulation, largely on non-vitamin K antagonist oral anticoagulants (NOACs).. Increased 8-isoprostane levels partly through altered fibrin clot structure are associated with thromboembolic events despite anticoagulant therapy in AF patients.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dinoprost; Female; Fibrin; Hemorrhage; Humans; Risk Factors; Stroke; Thromboembolism; Thrombosis; von Willebrand Factor

Platelets play an important role in both physiological hemostasis and pathological thrombosis. Thromboxane (TX) A

Topics: Animals; Bleeding Time; Blood Platelets; Cyclic AMP; Dinoprost; Female; Hemostasis; Humans; Inositol Phosphates; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation; Receptors, Prostaglandin E, EP3 Subtype; Receptors, Thromboxane A2, Prostaglandin H2; Thromboembolism

Several patient characteristics have been shown to increase the risk of inadequate platelet inhibition by aspirin, yet underlying mechanisms remain mostly unknown. We explored whether oxidative stress, via isoprostane formation, was associated with inadequate platelet response to aspirin. Additionally, we sought to investigate whether individual pre-selected demographic, hematological or biochemical parameters further increased the risk of inadequate platelet response to aspirin.. Two hundred consecutive subjects suffering from stable coronary artery disease and under daily aspirin therapy were enrolled in our study. Inadequate platelet response to aspirin was defined as residual platelet aggregation>or=20% per arachidonic acid-induced light transmission aggregometry. Morning urinary samples were used to determine levels of isoprostanes (8-iso-PGF2alpha) using an enzyme immunoassay.. Eight subjects were deemed to present inadequate platelet response to aspirin. Wide intersubject variability was observed in urinary 8-iso-PGF2alpha levels. However, levels were similar between aspirin responders and non-responders. Patients with inadequate platelet response to aspirin had higher platelet counts and received the lowest daily aspirin dose when compared to responders, suggesting subtherapeutic aspirin therapy due to increased platelet production. Only platelet count remained independently predictive of inadequate platelet response to aspirin in a multiple logistic regression model.. Urinary 8-iso-PGF2alpha levels, a reflection of systemic oxidative stress, did not appear to contribute to impaired platelet responsiveness to aspirin, while increased platelet production may partly explain this phenomenon.

Topics: Aged; Aspirin; Blood Platelets; Coronary Artery Disease; Dinoprost; Drug Resistance; Female; Humans; Male; Middle Aged; Oxidative Stress; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Risk Factors; Thromboembolism; Treatment Failure