Clinical associations with venous thromboembolism in anti-neutrophil cytoplasm antibody-associated vasculitides

Kronbichler, Andreas; Leierer, Johannes; Leierer, Gisela; Mayer, Gert; Casian, Alina; Höglund, Peter; Westman, Kerstin; Jayne, David

doi:10.1093/rheumatology/kew465

Cited by 27 publications

(48 citation statements)

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“…Moreover, we identified a trend toward an association between VTE and disease activity. A recent analysis of 417 patients from several randomized trials demonstrated an association between higher disease activity and VTE events , reinforcing the role of active vasculitis in predisposing individuals to thrombosis.…”

Section: Discussionmentioning

confidence: 85%

“…Analysis of a large cohort of patients with eosinophilic granulomatosis with polyangiitis (EGPA), GPA, and MPA demonstrated occurrence of VTE in 8.2%, 8.0%, and 7.8% of patients, respectively . More recently, analysis of data derived from several trials conducted by the European Vasculitis Society showed the occurrence of VTE in 41 (9.8%) of 417 patients with GPA or MPA . While VTE is now acknowledged as a commonly occurring complication of AAV, its pathogenesis remains ill‐defined.…”

Section: Introductionmentioning

confidence: 99%

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

Kronbichler

Leierer

Smıth

et al. 2019

Arthritis & Rheumatology

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ObjectiveTo 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.ConclusionPatients 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.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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

Kronbichler

Leierer

Smıth

et al. 2019

Arthritis & Rheumatology

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“…Schließlich haben Patienten mit aktiver Vaskulitis ein deutlich erhöhtes Thromboserisiko (8-10 %) [52,53], sodass bei langer Hospitalisierung und bei geringem Blutungsrisiko an eine prophylaktische Antikoagulation jedenfalls gedacht werden sollte. Während der initialen Phase der Erkrankung (hohe Steroiddosis, additive Immunsuppression und Aktivität der Grunderkrankung) ist eine antibiotische Prophylaxe mit Trimethoprim-Sulfamethoxazol sinnvoll [24,54].…”

Section: Erhaltungstherapie -Was Wird Empfohlen?unclassified

Nierenbeteiligung bei ANCA-assoziierten Vaskulitiden

Kronbichler

Windpessl

2019

Akt Rheumatol

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ZusammenfassungANCA-assoziierte Vaskulitiden sind seltene Kleingefäßvaskulitiden, wobei die jährliche Inzidenz in etwa bei 20 pro 1 000 000 Einwohner liegt. Eine Nierenbeteiligung kommt bei über 50% der betroffenen Patienten vor und geht mit Morbidität und Mortalität einher. Ein Screening auf Nierenbeteiligung sollte zum Zeitpunkt der Erstdiagnose und periodisch im Verlauf stattfinden. Eine Nierenbiopsie hat nicht nur einen diagnostischen Nutzen, sondern ist essentiell zur Prognoseabschätzung. Verschiedene histologische Kriterien sind in den letzten Jahren entwickelt worden, welche in den klinischen Alltag Einzug finden werden. Neben glomerulären Veränderungen scheinen für die Langzeitprognose auch tubulointerstitielle Veränderungen von Interesse zu sein. Die Therapie der ANCA-assoziierten Vaskulitis, sowohl in der Induktions- als auch in Erhaltungstherapie, wurde durch Rituximab verändert. Strategien zur Glucocorticoidreduktion bzw. -elimination wurden entwickelt, welche die Nebenwirkungen von Steroiden minimieren sollen. Da eine eingeschränkte Nierenfunktion das kardiovaskuläre Risiko von Patienten mit ANCA-assoziierter Vaskulitis deutlich erhöht, muss auf eine adäquate Kontrolle dieser Faktoren geachtet werden. Zudem haben Patienten während aktiver Phasen der Erkrankung ein hohes thromboembolisches Risiko und bei dementsprechenden Beschwerden sollte frühzeitig ein Screening stattfinden. Zusammengefasst hat das zunehmende wissenschaftliche Interesse auf dem Gebiet der Vaskulitiden dazu geführt, dass die Diagnostik und Therapie über das letzte Jahrzehnt deutlich optimiert wurde. Weitere Studien werden in der Zukunft „maßgeschneiderte“ therapeutische Behandlungen erlauben.

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“…A large retrospective cohort study of AAV subtypes found VTE incidences of 8.2% among patients with eosinophilic granulomatosis with polyangiitis (EGPA), 8% among patients with GPA, and 7.6% among patients with microscopic polyangiitis (MPA) (5). A recent study of trial data from the European Vasculitis Study group found c-reactive protein (CRP), cutaneous involvement, gastrointestinal involvement, and worsening renal function to be associated with increased risk of VTE among patients with GPA and MPA (6). Patients with AAV also have a greater risk of cardiovascular events, such as acute coronary syndrome, new onset angina, peripheral vascular disease, and transient ischemic attacks, which can be seen in patients with prothrombotic states (7).…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have sought to uncover molecular determinants of active vasculitis. There is increased recognition that antibodies against proteinase-3 (PR3) correlates well with the incidence of VTE (6,8). A slightly older study, however did note a protective effect of PR3 ANCA (1).…”

Section: Introductionmentioning

confidence: 99%

Venous Thrombotic Events in ANCA-Associated Vasculitis: Incidence and Risk Factors

et al. 2020

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Background. The incidence of venous thromboembolism (VTE) is increased in ANCA associated vasculitis (AAV). We assessed the frequency of VTE observed among patients with AAV evaluated at our center and identified risk factors. Methods. Patients from the Johns Hopkins Vasculitis Center cohort who were evaluated between 1998 and 2018 and had a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were eligible for analysis. Baseline demographics, clinical and serologic data were extracted. Univariate and multivariate analyses were performed to identify factors associated with VTE in AAV. Results. One hundred and sixty two patients with AAV were identified, 105 (65%) with GPA; 22 (14%) of these patients had a recorded VTE with a median time to VTE of 1 month. The mean (SD) age in the VTE versus non-VTE groups was 54 ± 20 versus 55 ± 17 years (p=0.99), 64% versus 60% female (p=0.93), 82% versus 49% PR3-ANCA positive (p=0.01), with a total mean BMI of 33.3 ± 5.7 versus 28.3 ± 6.1 kg/m 2 , (p<0.001) respectively. The median Birmingham Vasculitis Activity Score (BVAS version 3) was 19 versus 14 (p=0.02). Univariate analyses identified PR3 ANCA, rapidly progressive glomerulonephritis (RPGN), and hypoalbuminemia. In multivariate analysis, the significant associations with VTE included PR3-ANCA (OR 4.77, p=0.02), hypoalbuminemia (OR 4.84, p=0.004), and BMI (OR 1.18, p<0.001). Conclusion. VTE is a surprisingly common complication of AAV. PR3-ANCA and hypoalbuminemia are risk factors for developing VTEs. Further studies are needed to confirm these findings.

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Clinical associations with venous thromboembolism in anti-neutrophil cytoplasm antibody-associated vasculitides

Cited by 27 publications

References 22 publications

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

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

Nierenbeteiligung bei ANCA-assoziierten Vaskulitiden

Venous Thrombotic Events in ANCA-Associated Vasculitis: Incidence and Risk Factors

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