#1633 Increased levels of tissue factor is associated with upregulation of d-dimer and decreased levels of thrombin generation in end stage renal disease

Abstract Background and Aims End-stage renal disease (ESRD) is often associated with vascular complications. Tissue factor (TF) plays a very important role in triggering the thrombogenesis and biomarkers associated with thrombin generation (TG) such as D-Dimer (DD). TF levels in chronic kidney disease are known to be upregulated, however such a study in ESRD patients is not reported. In this study, we sought to measure TF antigen and activity levels, and their association with DD and TG potential. Method 72 patients plasma with confirmed ESRD was collected in the Hemodialysis Clinic at Loyola University Medical Center (LUMC). 50 plasma samples from a commercial source and 12 plasma samples from LUMC served as a control. Commercially available sandwich ELISA methods were used for TF antigen and DD levels, while a chromogenic substrate method was used to measure TF activity. TG was quantified by using a fluorogenic method. Applicable statistical methods were performed and p<0.05 were considered significant. Results ESRD patients showed marked increase in TF and DD levels compared to the control. DD increased from 121.1 to 905.8 ng/mL (7.5-fold, P < 0.05) and TF concentration increased from 107.5 to 283.6 pg/mL (2.6-fold, P < 0.05). Peak thrombin levels reduced in the patient cohort from 138.4 to 109.9 nM (−1.26-fold, P < 0.05), while lag time increased from 1.7 to 2 minutes (1.2-fold, P < 0.05). TF activity and ETP showed no significant difference. Table 1 represents the composite results in the patient cohort and controls. Conclusion These studies demonstrate that while TF activity is undetectable, TF antigen is quantifiable in ESRD patients. Simultaneously, the peak thrombin level decreased and DD levels increased. These results suggest that coagulation system is activated where thrombin is consumed leading to DD formation. Thus, TF upregulation plays a central role in the pathogenesis of ESRD and its measurement may be helpful in prognostic management.