Thrombin Generation Assay Detects Moderate-Intensity Statin-Induced Reduction of Hypercoagulability in Diabetes

Abstract

Statins not only have a lipid-lowering effect but also reduce inflammation and have an antithrombotic effect. Since hypercoagulability assessed by thrombin generation assay (TGA) and increased formation of neutrophil extracellular traps (NET) were demonstrated in diabetes, we investigated whether statin therapy in diabetes modifies coagulation status and NET formation. Twenty-five consecutive patients with diabetes were recruited. Global coagulation assays (prothrombin time [PT], activated partial thromboplastin time [aPTT], and TGA) and NET markers (DNA–histone complex, cell-free DNA, and neutrophil elastase) were measured before and after 3-month moderate-intensity statin therapy. In addition, all coagulation factors and 3 anticoagulation factors were measured. Statin therapy significantly reduced endogenous thrombin potential (ETP) value and blood lipids but did not change the PT and aPTT values or NET formation markers. Statin significantly decreased not only coagulation factors (II, V, VIII, IX, and X) but also the anticoagulation factor antithrombin. Statin-induced reduction of factor V and X significantly contributed to the reduction of ETP value. The extent of reduction in coagulation factors correlated with that of anticoagulation factors, but not that of cholesterol. It is possible to use TGA as a global coagulation assay that can detect coagulation status modified by statin therapy. Additional studies are needed to evaluate the clinical implications of statin-induced simultaneous reduction of coagulation and anticoagulation factors.