PO:37:269 | Intensive therapeutic plasma exchange in life-threatening ANCA-associated vasculitis

Davide Bertelle, Riccardo Bixio, Francesco Pollastri, Maurizio Rossini, Angelo Fassio, Alessandro Giollo | Unità di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa

Background. In ANCA-associated vasculitis (AAV), despite the findings of the PEXIVAS trial, the usefulness of plasma exchange (PLEX) remains debated in selected clinical settings, such as diffuse alveolar hemorrhage (DAH).

Methods. We report a case of life-threatening AAV successfully treated with an intensive, high-volume, and individualized PLEX protocol.

Results. We describe a 40-year-old man with newly diagnosed AAV (c-ANCA/anti-PR3, high titer) who presented with rapidly progressive glomerulonephritis and severe respiratory failure (PaO2/FiO2 ratio < 200) secondary to DAH, requiring mechanical ventilation. In addition to induction therapy with methylprednisolone pulses (total 3000 mg) and weekly rituximab (375 mg/m²), we initiated an intensive PLEX regimen consisting of 20 sessions over 52 days (three consecutive at onset), with a mean plasma exchange volume of 1.0–1.5 times the plasma volume (mean exchanged volume per session: 4450 ± 705 mL; total exchanged volume: 89 L). From the third PLEX session, we observed a marked reduction in ANCA titer and inflammatory markers, followed by significant respiratory improvement after the sixth session (Figure 1). The last four sessions were performed after extubation. At 48 months of follow-up, under maintenance therapy with mycophenolate mofetil, no vasculitis flares were observed, although renal recovery was not achieved. This case highlights the potential benefit of an intensive, high-volume PLEX protocol in life-threatening AAV with DAH, supporting several considerations: the PEXIVAS trial, cornerstone of current guidelines, adopted a limited PLEX schedule (7 sessions) without escalation in refractory cases—possibly underestimating efficacy in severe disease phenotypes (our patient achieved pulmonary recovery after the 6th session). Moreover, only 61 patients (8.7%) in PEXIVAS had DAH, and subgroup analysis showed lower one-year mortality in PLEX-treated patients (19.4% vs. 33.3%). A post-hoc analysis of PLEXIVAS demonstrated improved eGFR recovery at 4–8 weeks and greater renal recovery at one year in patients receiving PLEX. Although these findings are not generalizable, they retain potential clinical significance in selected severe cases. The KDIGO 2024 guidelines currently support PLEX in patients with serum creatinine ≥ 300 µmol/L (3.4 mg/dL), suggesting a tailored, individualized approach.

Conclusions. Intensive and personalized PLEX regimens deserve renewed consideration in life-threatening AAV—especially in patients with DAH, rapidly progressive renal involvement, or refractoriness to conventional therapy. The efficacy of PLEX in these settings cannot be fairly dismissed based on the PEXIVAS trial alone.