A New Multimodal and Semi-specific Therapeutic Plasmapheresis Concept, a Case Series Study

Overview

Global demand for therapeutic plasmapheresis is rising to treat various immunological, rheological, and lipoprotein-related disorders. Traditional therapeutic plasma exchange (TPE) removes plasma entirely and replaces it with costly substitution fluids, making it less sustainable. Semi-specific methods like plasma adsorption and double-filtration plasmapheresis (DFPP) avoid this by purifying and reinfusing the patient's own plasma. DFPP, although effective and widely reimbursed in Europe and Asia, relies on membrane-based plasma separation systems that require high blood flow rates and offer limited plasma extraction efficiency, which prolongs treatment and often necessitates central venous access. Centrifugation-based systems allow lower blood flow rates and higher plasma extraction ratios, but existing devices are not designed for automated double-cascade plasmapheresis. To address these limitations, our department has implemented a new strategy: Centrifugation and Filtration Plasmapheresis (CFPP), which combines centrifugation for initial plasma separation with membrane filtration for secondary purification. CFPP maintains the safety and efficacy of DFPP while offering key advantages: easier peripheral venous access, shorter procedures, no need for replacement fluids, and reinfusion of purified autologous plasma.

The global demand for specific and semi-specific therapeutic plasmapheresis is steadily increasing to address immunological disorders ("immunoapheresis"), rheological and microvascular disorders ("rheopheresis"), and lipoprotein disorders ("lipoprotein apheresis"). These procedures require plasma to be separated from the cellular components of blood. Once separated, plasma can either be entirely removed and replaced with a substitution fluid-referred to as therapeutic plasma exchange (TPE)-a non-specific apheresis method that is costly and unsustainable due to the use of valuable fluids such as fresh frozen plasma or human albumin; or it can be treated using semi-specific or specific methods. This secondary treatment can involve adsorption columns (plasma adsorption) or semi-specific filtration membranes, known as double-filtration plasmapheresis (DFPP) or double-cascade plasmapheresis. DFPP is a safe, efficient, and multimodal semi-specific plasmapheresis technique that is reimbursed in Europe and Asia, but surprisingly not in the United States. It is performed using certified automated devices such as the Plasauto® (Asahi®) or the HF440® (Infomed®), which use membrane filtration for initial plasma separation. However, this approach requires high blood flow rates (at least 80 mL/min), making peripheral venous access challenging. Additionally, the plasma extraction ratio is limited to approximately 33%, thereby prolonging the procedure. In contrast, centrifugation-based plasma separation enables lower blood flow rates (as low as 40 mL/min) and achieves higher plasma extraction ratios (up to 60%), facilitating the use of peripheral venous access and reducing procedure duration. Unfortunately, current certified centrifugation-based systems-such as the Optia® (Terumo®) and the Comtech® (Fresenius®)-are not designed for automated double-cascade plasmapheresis. To overcome these limitations, our team in Metz has implemented a custom technical setup that combines initial plasma separation by centrifugation (using the Optia® system) with secondary plasma treatment via membrane filtration (using Cascadeflo-EC® or Rheofilter® from Asahi®). We have termed this approach Centrifugation and Filtration Plasmapheresis (CFPP). CFPP is as safe and effective as DFPP, while integrating the advantages of centrifugation (lower blood flow, reduced need for central venous access, shorter treatment time) with the benefits of double-cascade plasmapheresis (semi-specific plasma purification, no need for fluid replacement, and reinfusion of the patient's own purified plasma).