Glucose Concentration Affects Fibrin Clot Structure and Morphology as Evidenced by Fluorescence Imaging and Molecular Simulations

Abstract

Although in vivo studies have been conducted in the past to determine hyperglycemic effects and influence on clotting risk in patients with diabetes, the true extent of hyperglycemia on unstable and spontaneous clot formation remains highly debated. Factors such as increased glycation, elevated fibrinogen concentration, elevated prothrombin levels, and decreased plasminogen are known to influence fibrin conversion, clot morphology, and thrombus formation in these individuals. In this regard, the isolated effects of hyperglycemia on irregular fibrin clot formation were investigated in a controlled fibrinogen system. In this study, fibrin clot characteristic differences at 3 glucose concentrations were analyzed to determine the effects of glucose concentration on fibrinogen glycation and fibrin clot morphology using confocal microscopy, glycation quantification, molecular simulations, and image processing methods. Algorithms coupled with statistical analysis support in vivo findings that hyperglycemia increases fibrinogen glycation, with ensuing altered fibrin clot structure characteristics. Our experimental and molecular simulation results consistently show an increased glucose adsorption by fibrinogen with increased glucose concentration. Significant differences in clot structure characteristics were observed, and the results of this work can be used to further develop diagnostic tools for evaluating clotting risk in individuals with hypercoagulable and hyperglycemic conditions.