title: Assays of fibrin network properties altered by VKAs in atrial fibrillation - importance of using an appropriate coagulation trigger.
abstract: Atrial fibrillation (AF) is a prothrombotic condition, involving increased thrombin generation and fibrinogen concentrations. Vitamin K antagonists (VKAs) prevent arterial thromboembolism if optimal anticoagulation is achieved by individualised drug doses, assessed by determining the Prothrombin time-related International Normalized Ratio (Pt-INR). There is evidence that formation of tight-laced fibrin networks is pathogenic in prothrombotic diseases. This study was performed among AF patients, to test whether long-term treatment with VKAs affects the structure of fibrin networks, and whether the effect is altered by employing different coagulation triggers: exogenous thrombin (1 IU/ml), 10 pM tissue factor (TF) or a commercial Pt-INR reagent (containing 400-fold more TF). In the thrombin-based method, fibrin network porosity (scanning electron microscopy) and liquid permeability (flow measurements) correlated inversely to fibrinogen concentrations, while positive correlations to the degree of anticoagulation were shown with the Pt-INR reagent. In the method with 10 pM TF, the two above relationships were detected, though the influence of Pt-INR was more profound than that of fibrinogen concentrations. Moreover, greater shortening of clot lysis time (CLT) arose from more permeable clots. As a coagulation trigger, 10 pM TF vs exogenous thrombin or the Pt-INR reagent is more informative in reflecting the in vivo process from thrombin generation to fibrin formation. Since fibrin network permeability rose in parallel to elevations of INR and shortening of CLT in AF patients, antithrombotic effects on prevention of thrombotic complications may be achieved from impairment of thrombin generation, resulting in formation of permeable clots susceptible to fibrinolysis.
authors.forename: Michal
authors.initials: M
authors.lastname: Ząbczyk
authors.forename: Margareta
authors.initials: M
authors.lastname: Blombäck
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Karkowski
authors.forename: Hakan N
authors.initials: HN
authors.lastname: Wallen
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
authors.affiliation: Shu He, MD, PhD, Building 8-9, 6th floor, Danderyds Hospital, 182 88 Stockholm, Sweden, Tel.: 46+762115129, Fax: 46+812356187, E-mail: heshu9999@gmail.com.
authors.forename: Shu
authors.initials: S
authors.lastname: He
mesh_terms: D000074:Acenocoumarol / Q000627:therapeutic use*; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D001777:Blood Coagulation / Q000187:drug effects*; D016022:Case-Control Studies; D005337:Fibrin / Q000378:metabolism* / Q000648:ultrastructure; D063285:Fibrin Clot Lysis Time; D006801:Humans; D019934:International Normalized Ratio; D008855:Microscopy, Electron, Scanning; D011044:Poland; D016062:Porosity; D011487:Protein Conformation; D013548:Sweden; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D014812:Vitamin K / Q000037:antagonists & inhibitors* / Q000097:blood; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin; D005337:Fibrin; D013917:Thrombin; D000074:Acenocoumarol
keywords: Atrial fibrillation; Pt-INR; coagulation trigger; fibrin network permeability; vitamin K antagonists