Abstract:

Objective: To investigate the ability to remove different plasma proteins by double-filtration plasmapheresis (DFPP) using various primary separator and secondary separator combinations; based on it, to propose a novel DFPP therapy, and test its ability to eliminate MPO-ANCA from circulation of patients with vasculitides.  Methodology: Sixteen patients with serum MPO-ANCA positive diagnosed as vasculitides were enrolled and received 44 sessions DFPP. Three kinds of plasma filters were used to serve as primary and secondary filter, one plasma separator MPS07 and two plasma fraction separators EC50W, EC20W. There were three combinations: MPS07/EC50W, MPS07/EC20W, and EC50W/EC20W combination; in each combination, the former was used as primary filter, and the latter was used as secondary filter. Double volume of plasma was processed, and 30~40g human albumin was supplemented during each session. One received 3 sessions DFPP using MPS07/EC50W, 9 received 27 sessions DFPP using MPS07/EC20W, and the other 5 patients received 14 sessions DFPP using EC50W/EC20W. During DFPP, waste plasma was discarded in intermittent way. When the pressure pre-secondary filter reached the threshold value to discard plasma, 800ml normal saline was flushing the secondary filter to force filtration of plasma proteins accumulated in filter, before waste plasma was discarded. Sieving coefficients (SC) of albumin, IgA, IgG and IgM were measured for 3 filters, as well as reduction percentage of plasma proteins concentrations, MPO-ANCA titer by single session DFPP. Results: MPS07 filter was well permeable for all above-mentioned plasma proteins (SC>0.6); while EC50W filter was well permeable for albumin and IgG, less permeable for IgA, and little permeable for IgM (SC 0.06); EC20W filter was permeable for only small proportion of albumin and IgG, much less for IgA, and impermeable for IgM (SC 0.03). Single session of DFPP had no effect on serum albumin level, but had diverse effects on other proteins concentration depending on filters combinations and proteins’ type. During DFPP using MPS07/EC50W, decline of IgM, IgA, and IgG was （89.7±5.4）%, （61.7±14.8）%, and（30.5±9.0）% respectively. During DFPP using MPS07/EC20W, decline of IgM, IgA, and IgG was（94.2±3.1）%, （96.2±2.3）%, and （64.7±21.0）% respectively. During DFPP using EC50W/EC20W, decline of IgM, IgA, and IgG was （2.80±12.9）%, (90.9±4.4)%, and (43.5±13.8)%, respectively. Reduction percentage of MPO-ANCA titer by single session DFPP using EC50W/EC20W was (34.6±14.3)%. Forced filtration of plasma in secondary filter by normal saline flushing before waste plasma discarding could raise the ratio of IgG/albumin concentration in waste plasma by 24.2%.  Conclusions: According to sieving coefficients of three kinds of filters for different plasma proteins, DFPP using EC50W/EC20W filters is better for removal of pathogens like IgG. With more selective removal of IgG, less loss of other larger useful molecules, it is effective to reduce serum ANCA titer.