Association of Pulmonary Hemorrhage, Positive Proteinase 3, and Urinary Red Blood Cell Casts With Venous Thromboembolism in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

the RAVE−ITN Research Group

Research output: Contribution to journalArticle

Abstract

Objective: To assess the frequency of venous thromboembolism (VTE) events in the Rituximab in Antineutrophil Cytoplasmic Antibody (ANCA)–Associated Vasculitis (RAVE) trial and identify novel potential risk factors. Methods: VTE events in 197 patients enrolled in the RAVE trial were analyzed. Baseline demographic and clinical characteristics were recorded, and univariate and multivariate analyses were performed to identify factors associated with VTE in ANCA-associated vasculitis (AAV). Results: VTE occurred in 16 patients (8.1%) with an overall average time to event of 1.5 months (range 1.0–2.75). In univariate analyses with calculation of hazard ratios (HRs) and 95% confidence intervals (95% CIs), heart involvement (HR 17.408 [95% CI 2.247–134.842]; P = 0.006), positive proteinase 3 (PR3)–ANCA (HR 7.731 [95% CI 1.021–58.545]; P = 0.048), pulmonary hemorrhage (HR 3.889 [95% CI 1.448–10.448]; P = 0.008), and the presence of red blood cell casts (HR 15.617 [95% CI 3.491–69.854]; P < 0.001) were associated with the onset of VTE. In multivariate models adjusted for age and sex, the significant associations between VTE events and heart involvement (HR 21.836 [95% CI 2.566–185.805]; P = 0.005), PR3-ANCA (HR 9.12 [95% CI 1.158–71.839]; P = 0.036), pulmonary hemorrhage (HR 3.91 [95% CI 1.453–10.522]; P = 0.007), and urinary red blood cell casts (HR 16.455 [95% CI 3.607–75.075]; P < 0.001) remained. Conclusion: Patients diagnosed as having AAV with pulmonary hemorrhage, positive PR3-ANCA, heart involvement, and the presence of red blood cell casts are at an increased risk to develop VTE. Further studies are needed to confirm and expand these findings and to explore the mechanisms of hypercoagulability in these patients with the aim of informing potential targets for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)1888-1893
Number of pages6
JournalArthritis and Rheumatology
Volume71
Issue number11
DOIs
StatePublished - Nov 1 2019

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Myeloblastin
Venous Thromboembolism
Vasculitis
Erythrocytes
Confidence Intervals
Antineutrophil Cytoplasmic Antibodies
Hemorrhage
Lung
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Thrombophilia
Multivariate Analysis
Demography

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

@article{9812038502264f4e8e54c75d1f2363fe,
title = "Association of Pulmonary Hemorrhage, Positive Proteinase 3, and Urinary Red Blood Cell Casts With Venous Thromboembolism in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis",
abstract = "Objective: To assess the frequency of venous thromboembolism (VTE) events in the Rituximab in Antineutrophil Cytoplasmic Antibody (ANCA)–Associated Vasculitis (RAVE) trial and identify novel potential risk factors. Methods: VTE events in 197 patients enrolled in the RAVE trial were analyzed. Baseline demographic and clinical characteristics were recorded, and univariate and multivariate analyses were performed to identify factors associated with VTE in ANCA-associated vasculitis (AAV). Results: VTE occurred in 16 patients (8.1{\%}) with an overall average time to event of 1.5 months (range 1.0–2.75). In univariate analyses with calculation of hazard ratios (HRs) and 95{\%} confidence intervals (95{\%} CIs), heart involvement (HR 17.408 [95{\%} CI 2.247–134.842]; P = 0.006), positive proteinase 3 (PR3)–ANCA (HR 7.731 [95{\%} CI 1.021–58.545]; P = 0.048), pulmonary hemorrhage (HR 3.889 [95{\%} CI 1.448–10.448]; P = 0.008), and the presence of red blood cell casts (HR 15.617 [95{\%} CI 3.491–69.854]; P < 0.001) were associated with the onset of VTE. In multivariate models adjusted for age and sex, the significant associations between VTE events and heart involvement (HR 21.836 [95{\%} CI 2.566–185.805]; P = 0.005), PR3-ANCA (HR 9.12 [95{\%} CI 1.158–71.839]; P = 0.036), pulmonary hemorrhage (HR 3.91 [95{\%} CI 1.453–10.522]; P = 0.007), and urinary red blood cell casts (HR 16.455 [95{\%} CI 3.607–75.075]; P < 0.001) remained. Conclusion: Patients diagnosed as having AAV with pulmonary hemorrhage, positive PR3-ANCA, heart involvement, and the presence of red blood cell casts are at an increased risk to develop VTE. Further studies are needed to confirm and expand these findings and to explore the mechanisms of hypercoagulability in these patients with the aim of informing potential targets for therapeutic intervention.",
author = "{the RAVE−ITN Research Group} and Andreas Kronbichler and Johannes Leierer and Shin, {Jae Il} and Merkel, {Peter A.} and Robert Spiera and Philip Seo and Langford, {Carol A.} and Hoffman, {Gary S.} and Kallenberg, {Cees G.M.} and St.Clair, {E. William} and Paul Brunetta and Fervenza, {Fernando C.} and Duvuru Geetha and Keogh, {Karina A.} and Monach, {Paul A.} and Ytterberg, {Steven R.} and Gert Mayer and Ulrich Specks and Stone, {John H.}",
year = "2019",
month = "11",
day = "1",
doi = "10.1002/art.41017",
language = "English (US)",
volume = "71",
pages = "1888--1893",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "11",

}

TY - JOUR

T1 - Association of Pulmonary Hemorrhage, Positive Proteinase 3, and Urinary Red Blood Cell Casts With Venous Thromboembolism in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

AU - the RAVE−ITN Research Group

AU - Kronbichler, Andreas

AU - Leierer, Johannes

AU - Shin, Jae Il

AU - Merkel, Peter A.

AU - Spiera, Robert

AU - Seo, Philip

AU - Langford, Carol A.

AU - Hoffman, Gary S.

AU - Kallenberg, Cees G.M.

AU - St.Clair, E. William

AU - Brunetta, Paul

AU - Fervenza, Fernando C.

AU - Geetha, Duvuru

AU - Keogh, Karina A.

AU - Monach, Paul A.

AU - Ytterberg, Steven R.

AU - Mayer, Gert

AU - Specks, Ulrich

AU - Stone, John H.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Objective: To assess the frequency of venous thromboembolism (VTE) events in the Rituximab in Antineutrophil Cytoplasmic Antibody (ANCA)–Associated Vasculitis (RAVE) trial and identify novel potential risk factors. Methods: VTE events in 197 patients enrolled in the RAVE trial were analyzed. Baseline demographic and clinical characteristics were recorded, and univariate and multivariate analyses were performed to identify factors associated with VTE in ANCA-associated vasculitis (AAV). Results: VTE occurred in 16 patients (8.1%) with an overall average time to event of 1.5 months (range 1.0–2.75). In univariate analyses with calculation of hazard ratios (HRs) and 95% confidence intervals (95% CIs), heart involvement (HR 17.408 [95% CI 2.247–134.842]; P = 0.006), positive proteinase 3 (PR3)–ANCA (HR 7.731 [95% CI 1.021–58.545]; P = 0.048), pulmonary hemorrhage (HR 3.889 [95% CI 1.448–10.448]; P = 0.008), and the presence of red blood cell casts (HR 15.617 [95% CI 3.491–69.854]; P < 0.001) were associated with the onset of VTE. In multivariate models adjusted for age and sex, the significant associations between VTE events and heart involvement (HR 21.836 [95% CI 2.566–185.805]; P = 0.005), PR3-ANCA (HR 9.12 [95% CI 1.158–71.839]; P = 0.036), pulmonary hemorrhage (HR 3.91 [95% CI 1.453–10.522]; P = 0.007), and urinary red blood cell casts (HR 16.455 [95% CI 3.607–75.075]; P < 0.001) remained. Conclusion: Patients diagnosed as having AAV with pulmonary hemorrhage, positive PR3-ANCA, heart involvement, and the presence of red blood cell casts are at an increased risk to develop VTE. Further studies are needed to confirm and expand these findings and to explore the mechanisms of hypercoagulability in these patients with the aim of informing potential targets for therapeutic intervention.

AB - Objective: To assess the frequency of venous thromboembolism (VTE) events in the Rituximab in Antineutrophil Cytoplasmic Antibody (ANCA)–Associated Vasculitis (RAVE) trial and identify novel potential risk factors. Methods: VTE events in 197 patients enrolled in the RAVE trial were analyzed. Baseline demographic and clinical characteristics were recorded, and univariate and multivariate analyses were performed to identify factors associated with VTE in ANCA-associated vasculitis (AAV). Results: VTE occurred in 16 patients (8.1%) with an overall average time to event of 1.5 months (range 1.0–2.75). In univariate analyses with calculation of hazard ratios (HRs) and 95% confidence intervals (95% CIs), heart involvement (HR 17.408 [95% CI 2.247–134.842]; P = 0.006), positive proteinase 3 (PR3)–ANCA (HR 7.731 [95% CI 1.021–58.545]; P = 0.048), pulmonary hemorrhage (HR 3.889 [95% CI 1.448–10.448]; P = 0.008), and the presence of red blood cell casts (HR 15.617 [95% CI 3.491–69.854]; P < 0.001) were associated with the onset of VTE. In multivariate models adjusted for age and sex, the significant associations between VTE events and heart involvement (HR 21.836 [95% CI 2.566–185.805]; P = 0.005), PR3-ANCA (HR 9.12 [95% CI 1.158–71.839]; P = 0.036), pulmonary hemorrhage (HR 3.91 [95% CI 1.453–10.522]; P = 0.007), and urinary red blood cell casts (HR 16.455 [95% CI 3.607–75.075]; P < 0.001) remained. Conclusion: Patients diagnosed as having AAV with pulmonary hemorrhage, positive PR3-ANCA, heart involvement, and the presence of red blood cell casts are at an increased risk to develop VTE. Further studies are needed to confirm and expand these findings and to explore the mechanisms of hypercoagulability in these patients with the aim of informing potential targets for therapeutic intervention.

UR - http://www.scopus.com/inward/record.url?scp=85073929585&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073929585&partnerID=8YFLogxK

U2 - 10.1002/art.41017

DO - 10.1002/art.41017

M3 - Article

C2 - 31216123

AN - SCOPUS:85073929585

VL - 71

SP - 1888

EP - 1893

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 11

ER -