Abstract: TH-PO057

Microparticle Tissue Factor Activity Dominates Venous Thromboembolism Signature in ANCA Vasculitis

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Mendoza, Carmen E., University of North Carolina, Chapel Hill, North Carolina, United States
  • Derebail, Vimal K., University North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Bunch, Donna O., UNC Kidney Center, Chapel Hill, North Carolina, United States
  • Brant, Elizabeth J., Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States
  • Mcdermott, Matthew L., University of North Carolina, Chapel Hill, North Carolina, United States
  • Froment, Anne B., UNC Kidney Center, Chapel Hill, North Carolina, United States
  • Hu, Yichun, UNC Kidney Center, Chapel Hill, North Carolina, United States
  • Hogan, Susan L., University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States
  • Jennette, J. Charles, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Falk, Ronald J., University of North Carolina Hospitals, Chapel Hill, North Carolina, United States
  • Nachman, Patrick H., University of North Carolina School of Medicine , Chapel Hill, North Carolina, United States
Background

Venous thromboembolism (VTE) is a complication of ANCA vasculitis whose mechanism remains incompletely elucidated. We tested biomarkers associated with disease activity in ANCA vasculitis and/or VTE in other diseases, including microparticle tissue factor activity (MPTFa) and anti-plasminogen (anti-Plg) to devise a thrombotic signature. We hypothesized that elevated MPTFa and anti-Plg may identify patients at risk for VTE.

Methods

Patients were enrolled during active disease. Twelve patients experienced a VTE (VTEpos) and were compared to patients without VTE (VTEneg, n=29) and 56 healthy controls (HC). Platelet free plasma and serum samples were assayed for MPTFa and anti-Plg. IL-6 was measured by a commercial ELISA; positivity was defined as 2 standard deviations above the HC mean. D-dimer, high sensitivity CRP (hs-CRP) and serum creatinine were measured by our clinical laboratory. Measures were assessed at active disease and remission. Univariate and bivariate analyses were performed by Cox regression.

Results

Demographics were similar in patients and HC. VTEpos and VTEneg patients did not differ in ANCA serotype, titer or BVAS. In univariate analysis, elevated MPTFa during active disease was associated with VTE (HR=1.06, 95%CI 1.01, 1.10; p=0.009). For every 10 units increase of MPTFa during active disease, the risk of VTE increased by 60%. This is a significant unit of measure as the threshold for positivity was set at 11% of the positive control. Assuming remission values before and after VTE are comparable, MPTFa at remission was also associated with VTE (HR=1.4, 95%CI 1.11, 1.77; p=0.005). Similarly, increased anti-Plg during remission was associated with VTE (HR=1.17, 95%CI 1.03, 1.33; p=0.02) but not at active disease. Per unit increases of both hs-CRP (HR=1.21, 95%CI 1.02, 1.45; p=0.04) and serum creatinine (HR=1.29, 95%CI 1.0, 1.66; p=0.05) were associated with VTE. IL-6 and D-dimer were not associated with VTE. In bivariate analysis, MPTFa adjusted for serum creatinine was still significantly associated with VTE (HR=1.05, 95%CI 1.01, 1.10; p=0.01).

Conclusion

Our data suggest that of the variables evaluated, elevated MPTFa provides the best marker of VTE and may identify patients at high risk for VTE in ANCA vasculitis.

Funding

  • NIDDK Support