Abstract: SA-PO929
Upregulation of Tissue Factor Is Associated with Increased Levels of D-dimer and Decreased Levels of Thrombin Generation in ESKD
Session Information
- Pathology and Lab Medicine - 2
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1800 Pathology and Lab Medicine
Authors
- Hussain, Hamzah, Loyola University Medical Center, Chicago, Illinois, United States
- Siddiqui, Fakiha, Loyola University Medical Center, Chicago, United States
- Hoppensteadt, Debra, Loyola University Medical Center, Chicago, Illinois, United States
- Fairand, Elyse, Loyola University Medical Center, Chicago, Illinois, United States
- Abulencia, Emma, Loyola University Medical Center, Chicago, Illinois, United States
- Fareed, Jawed, Loyola University Medical Center, Chicago, Illinois, United States
- Bansal, Vinod K., Loyola University Medical Center, Chicago, Illinois, United States
Background
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.
Methods
72 patients plasma with confirmed ESRD was collected in the Hemodialysis Clinic at Loyola University Medical Center (LUMC). 50 healthy plasma samples from a commercial source and 12 healthy plasma samples from LUMC served as control. Sandwich ELISA methods were used to measure TF antigen and DD levels and a chromogenic substrate method was used for 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 7.08 to 905.8ng/mL (128-fold, p<0.05) and TF concentration increased from 107.5 to 283.6pg/mL (2.6-fold, p<0.05). Peak thrombin levels reduced in the patient cohort from 138.4 to 109.9nM (-1.3-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.
Table 1
| Biomarkers | Controls Median (IQR) | ESRD Median (IQR) | p-value |
| DD (ng/mL) | 7.08 (7.08-44.4) | 905.8 (616.5-1831.4) | <0.05 |
| TF Immunologic (pg/mL) | 107.5 (60.2-125.1) | 283.6 (243.3-352.7) | <0.05 |
| TF Activity (optical density) | 0.08 (0.07-0.15) | 0.09 (0.07-0.12) | 0.66 |
| Peak Thrombin (nM) | 138.4 (126.6-155.6) | 109.9 (58.1-142.5) | <0.05 |
| Lag Time (min) | 1.7 (1.7-2.0) | 2.0 (1.6-2.3) | <0.05 |
| Endogenous Thrombin Potential (nM*min) | 583.7 (532.8-651.7) | 592.0 (388.5-704.2) | 0.46 |