Assessment of complement activation during membrane‐based plasmapheresis procedures

Abstract

Previous studies have suggested that plasmapheresis procedures using a separation membrane may activate the complement system and release anaphylatoxins. This study determines the content in C3a/C3a(des Arg) and C5a/C5a(des Arg) in plasma donations obtained by the new Haemonetics Filter Core (FC) procedure and compares it to Baxter Autopheresis C (Auto-C). FC performs sequential blood centrifugation and plasma filtration on a microporous polyethersulfone membrane, while Auto-C removes blood cells by simultaneous gravitation and filtration on a rotating nylon membrane. One group of 34 donors donated on FC and two groups of 30 and 10 donors on Auto-C. Plasma aliquots were taken from the plasma units within 30 min of the end of the collection procedures, frozen at < -30 degrees C and assessed for C3a and C5a at various time points of storage. Mean C3a/C3a(des Arg) in FC plasma (N = 34) was 1,151 (range: 526-2,991), 1,092 (range: 349-3498), and 507 (range: 307-815) ng/ml at time of collection and after 6 and 12 months of storage, respectively. Respective C5a/C5a(des Arg) was 26.6 (range 4.9-74), 18.9 (9.5-42.6), and 30.9 (range: 10.7-62.3) ng/ml. Mean C3a/C3a(des Arg) was higher in Auto-C (P < 0.001): 4,724 ng/ml (N = 10; range: 2,400-7 ,360) and > 4,149 ng/ml (N = 30; 2,408- > 6,430) after 3 and 18 months storage, respectively. Mean C5a/C5a(des Arg) was 32.1 ng/ml (N = 30; range: 10.6-57.2) after 18 months of storage. Complement activation in FC plasmas appears limited compared to Auto-C, suggesting better biocompatibility of this collection device and/or a favourable impact of the sequential cell centrifugation/filtration technology used. Further studies are needed to explain differences in complement activation between apheresis procedures and to assess clinical impacts, if any.

Modern Plasma Fractionation

“…Protein content and quality of fractionated proteins is apparently not affected by the apheresis system used, although residual cell content differ based upon the type and configuration of the cell separation device. 4 Plasma from membrane apheresis procedures, as does recovered plasma prepared from whole blood leukoreduced on positively charged filters, may 4Performed by most fractionators. yMandatory in Europe for HCV.…”

“…Because AAT shares many physicochemical properties, in particular, molecular weight and isoelectric point, with albumin, it has been difficult to design production methods for AAT not affecting the existing production process for albumin. Most preparations are recovered from fraction IV [1][2][3][4] . Purification from this waste fraction is rather cumbersome and involves PEG precipitation and ion-exchange chromatography, considerably compromising recovery (~0.2 g/L).…”

Clinical evaluation of polyethersulfone high‐flux hemodialysis membrane compared to other membranes

“…However, these membranes provide relatively little clearance for “middle” molecules and cause complement activation upon contacting with blood 2. Complement activation occurs during the interactions between the blood and various components of the hemodialysis membrane, which was defined as the bad biocompatibility and may adversely affect the patients and even lead to deleterious outcomes 3. What's more, among the chronic hemodialysis patients these interactions are repetitive and occur three times a week.…”

Post-bone marrow transplant thrombotic microangiopathy

“…However, PE can theoretically potentiate the effects of TMA by complement activation. 92,93 In 2011, eculizumab, the humanized monoclonal antibody, became the only therapy approved by the Food and Drug Administration for the management of aHUS. Eculizumab inhibits activation of the terminal complement pathway (C5), and its effectiveness in treating aHUS was demonstrated in many studies.…”