title: Laboratory assessment of anti-thrombotic therapy in heart failure, atrial fibrillation and coronary artery disease: insights using thrombelastography and a micro-titre plate assay of thrombogenesis and fibrinolysis.
abstract: As heart failure, coronary artery disease and atrial fibrillation all bring a risk of thrombosis, anti-thrombotic therapy is recommended. Despite such treatment, major cardiovascular events such as myocardial infarction and stroke still occur, implying inadequate suppression of thrombus formation. Accordingly, identification of patients whose haemostasis remains unimpaired by treatment is valuable. We compared indices for assessing thrombogenesis and fibrinolysis by two different techniques in patients on different anti-thrombotic agents, i.e. aspirin or warfarin. We determined fibrin clot formation and fibrinolysis by a microplate assay and thromboelastography, and platelet marker soluble P selectin in 181 patients with acute or chronic heart failure, coronary artery disease who were taking either aspirin or warfarin. Five thromboelastograph indices and four microplate assay indices were different on aspirin versus warfarin (p < 0.05). In multivariate regression analysis, only microplate assay indices rate of clot formation and rate of clot dissolution were independently related to aspirin or warfarin use (p ≤ 0.001). Five microplate assay indices, but no thrombelastograph index, were different (p < 0.001) in aspirin users. Three microplate assay indices were different (p ≤ 0.002) in warfarin users. The microplate assay indices of lag time and rate of clot formation were abnormal in chronic heart failure patients on aspirin, suggesting increased risk of thrombosis despite anti-platelet use. Soluble P selectin was lower in patients on aspirin (p = 0.0175) but failed to correlate with any other index of haemostasis. The microplate assay shows promise as a tool for dissecting thrombogenesis and fibrinolysis in cardiovascular disease, and the impact of antithrombotic therapy. Prospective studies are required to determine a role in predicting thrombotic risk.
authors.affiliation: University of Birmingham Institute for Cardiovascular Sciences City Hospital, Dudley Road, Birmingham, B18 7QH, UK.
authors.forename: Y C
authors.initials: YC
authors.lastname: Lau
authors.affiliation: University of Birmingham Institute for Cardiovascular Sciences City Hospital, Dudley Road, Birmingham, B18 7QH, UK.|Cardiovascular Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Xiong
authors.affiliation: University of Birmingham Institute for Cardiovascular Sciences City Hospital, Dudley Road, Birmingham, B18 7QH, UK.
authors.forename: P
authors.initials: P
authors.lastname: Ranjit
authors.affiliation: University of Birmingham Institute for Cardiovascular Sciences City Hospital, Dudley Road, Birmingham, B18 7QH, UK.
authors.forename: G Y H
authors.initials: GY
authors.lastname: Lip
authors.affiliation: University of Birmingham Institute for Cardiovascular Sciences City Hospital, Dudley Road, Birmingham, B18 7QH, UK. Andrew.blann@hotmail.com.
authors.forename: A D
authors.initials: AD
authors.lastname: Blann
mesh_terms: D001241:Aspirin / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy; D019411:Clinical Laboratory Techniques / Q000379:methods* / Q000592:standards; D003324:Coronary Artery Disease / Q000188:drug therapy; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006331:Heart Diseases / Q000188:drug therapy*; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D013916:Thrombelastography / Q000592:standards*; D013927:Thrombosis / Q000188:drug therapy; D046888:Tissue Array Analysis / Q000592:standards*; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D005343:Fibrinolytic Agents; D014859:Warfarin; D001241:Aspirin
keywords: Fibrinolysis; Haemostasis; Thrombelastograph; Thrombosis