Elevated Microparticle Tissue Factor Activity Differentiates Patients With Venous Thromboembolism in Anti-neutrophil Cytoplasmic Autoantibody Vasculitis

Carmen E. Mendoza, Elizabeth J. Brant, Matthew L. McDermott, Anne Froment, Yichun Hu, Susan L. Hogan, J. Charles Jennette, Ronald J. Falk, Patrick H. Nachman, Vimal K. Derebail, Donna O.Dell Bunch

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Introduction: Venous thromboembolism (VTE) is a life-threatening complication of anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis whose mechanism remains incompletely elucidated. We tested the hypothesis that elevated microparticle tissue factor activity (MPTFa) or anti-plasminogen antibodies (anti-Plg) may identify patients at risk for VTE. Methods: In this prospective study, patients were enrolled during active disease and followed longitudinally. Twelve patients who experienced a VTE (VTEpos) were compared with patients without VTE (VTEneg, n = 29) and healthy controls (HC, n = 70). MPTFa, anti-Plg, interleukin-6, high-sensitivity C-reactive protein (hs-CRP), D-dimer, serum creatinine, and serum albumin were assessed. Fisher's exact tests and Wilcoxon tests compared categorical and continuous variables, respectively. Cox regression for time to VTE or last follow-up was performed. Results: VTEpos patients had higher MPTFa (peak median = 14.0, interquartile range = 4.3–36.6) than HC (0, 0–3.5) and VTEneg patients (0, 0–1.4). In time-to-event analysis, MPTFa was associated with VTE when measured during both active disease (hazard ratio [HR]; 95% confidence interval [CI]: 1.04; 1.01–1.08) and remission (1.4; 1.11–1.77). Anti-Plg during remission was also associated with VTE (1.17; 1.03–1.33). Each g/dl decrease of serum albumin was associated with a 4-fold increase in VTE risk (4.4; 1.5–12.9). Adjusting for estimated glomerular filtration rate (eGFR), anti-Plg during remission remained significantly associated with VTE. Conclusion: Elevated MPTFa and increased anti-Plg in remission are strong indicators of VTE independent of renal function. Association of anti-Plg during remission with VTE implies hypercoagulability even during disease quiescence. Hypoalbuminemia strongly portends VTE risk, which is a novel finding in ANCA vasculitis. A thrombotic signature would allow improved management of patients to minimize VTE risk and complications of anticoagulation.

Original languageEnglish (US)
Pages (from-to)1617-1629
Number of pages13
JournalKidney International Reports
Volume4
Issue number11
DOIs
StatePublished - Nov 2019
Externally publishedYes

Keywords

  • autoimmunity
  • biomarkers
  • plasminogen
  • thrombosis
  • tissue factor
  • venous thrombosis

PubMed: MeSH publication types

  • Journal Article

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