Baseline and follow‐up blood samples were analyzed in cases and controls using the following methods: fibrinogen (clot‐rate assay, STA‐R instrument, Diagnostica Stago, Parsippany, NJ, USA), factor VIII and IX activity (clotting time on mixing with factor VIII or IX deficient plasma using STA‐Deficient VIII or IX; STA‐R instrument, Diagnostica Stago), von Willebrand factor, antithrombin and D‐dimer (immunoturbidometric or colorimetric assays, Liatest von Willebrand factor, Liatest D‐Di, Stachrom ATIII; STA‐R instrument, Diagnostica Stago), PAI‐1, PAP and prothrombin antigen (in‐house immunoassays),12, 13 prothrombin fragment 1.2 (ELISA, Dade Behring, Marburg, Germany), protein C antigen, free and total protein S antigen (Asserachrom ELISA, Diagnostica Stago), CRP (nephelometry, N High Sensitivity CRP, Dade‐Behring, Deerfield, IL, USA). Distributions of each biomarker were examined blind to case control status. Analytical outliers were defined based on knowledge of the biology and excluded from analysis as follows: factor VIIIc or prothrombin antigen <10%, fragment 1.2 > 7.2 nmol/L (>3 SD above the mean), PAI‐1 > 70 ng/mL.14
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