Introduction: Peripheral venous access (PVA) is recommended as a first-line vascular approach for therapeutic plasmapheresis with centrifugation methods but not filtration, which usually requires high blood flow. We evaluated the feasibility, efficacy, and safety of double-filtration plasmapheresis (DFPP) with PVA, using ultrasound guidance and regional citrate anticoagulation (RCA), i.e., PVA-RCA-DFPP in patients undergoing chronic DFPP. Secondly, we assessed the number of central venous catheters (CVCs) avoided. Methods: A single-center retrospective study evaluated 22 adult patients on chronic DFPP to perform PVA-RCA-DFPP. They were classified into 3 groups: successful (i.e., completion of sessions with PVA), primary failure (i.e., no sessions completed), secondary failure (i.e., ≥1 session with PVA completed but secondary return with CVC or arteriovenous fistula). Results: Among the 22 patients included (64% men), 7 patients (32%) were classified as primary failures (2 patient refusals, 5 inadequate PVAs), 1 patient (5%) as a secondary failure (due to uncomfortable venipunctures), and 14 patients (64%) as successful. In the successful group including 12 patients treated for chronic inflammatory demyelinating polyneuropathy (CIDP) and 2 patients for familial hypercholesterolemia (FH) (2 patients), 116 sessions were performed, with a median treated plasma volume of 4.3 L [IQR 3.6–4.6] (45 mL/kg) for a median duration of 134 min [IQR 122–144], and a median blood flow of 94 mL/min [IQR 87–103]. For the CIDP group, 90% of sessions achieved a plasma volume >1 TPV, and for the FH group 91% of sessions achieved an LDLc reduction >60%. Eleven sessions out of 116 (9%) were interrupted, mostly due to PVA dysfunction (5/11) and circuit clotting (4/11). Session interruptions decreased significantly between each patient’s first and following sessions (29% to 7%, p = 0.009). Conclusion: Chronic PVA-RCA-DFPP can be performed safely and efficiently, avoiding the use of CVCs.

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