People with ANCA-associated vasculitis (AAV) are at a greater risk of venous thromboembolism — blood clots in veins — if they have evidence of bleeding into the lungs, heart involvement, red blood cells in their urine, or anti-PR3-ANCA autoantibodies, according to a study in patients of a Phase 2/3 trial.
The research, “The Association of Pulmonary Haemorrhage, Positive PR3-ANCA and Urinary Red Blood Cell Casts with Venous Thromboembolism in ANCA-Associated Vasculitis,” was published in the journal Arthritis & Rheumatology.
As treatment options improve for AAV patients, complications likely due to immunosuppression or the disease itself are increasingly being addressed. Recent research has reported an increase in the frequency of venous thromboembolic events (VTEs) in these people.
Aiming to better understand this association and identify potential risk factors, an international team analyzed 197 patients who took part in the RAVE Phase 2/3 study (NCT00104299).
Forty-two participants (21.3%) were given anticoagulation prophylaxis (preventive) therapy. VTEs were defined as deep vein thrombosis (DVT), a pulmonary embolism — a blood clot starting in a deep vein, usually in the leg, then migrating and blocking a lung artery — or both.
This trial enabled researchers to follow people with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and also provided an opportunity to compare two treatment strategies — rituximab (brand name Rituxan, Truxima, and Ruxience, among others) and cyclophosphamide followed by azathioprine. Glucocorticoid use was tapered within 5.5 months in both groups.
VTEs occurred in 16 (8.1%) patients in the study: 11 with deep vein thrombosis, four with pulmonary embolism, and one person with both. Overall, the mean time from baseline (study start) to a VTE was 1.5 months. These patients had greater disease activity at baseline compared to those without such events, as assessed with the Birmingham Vasculitis Activity Score for GPA.
Among the group experiencing VTEs, the presence of anti-PR3-ANCA autoantibodies were more common than anti-MPO autoantibodies.
Researchers found that VTEs also associated with heart manifestations and pulmonary bleeding, as well as with testing positive for anti-PR3-ANCA autoantibodies and having urinary red blood cell casts. These correlations remained significant after accounting for age and sex.
Patients with VTEs were less likely to have eye involvement and sinusitis. No differences were found between newly diagnosed and relapsing patients across treatment groups.
“Patients with ANCA-associated vasculitis with pulmonary haemorrhage, positive PR3-ANCA, heart involvement and presence of red blood cell casts are at an increased risk to develop VTEs,” the investigators wrote.
While the association with lung bleeding, heart involvement, and red blood cells in the urine can reflect more severe disease, the presence of anti-PR3 antibodies may boost this risk through a greater presence of anti-plasminogen antibodies, which are known to contribute to VTEs, the investigators said.
Future studies are needed to address these findings and explore treatment targets, they added.