Complement activation during plasma production depends on the apheresis technique

Abstract

Elevated anaphylatoxin concentrations have been found in fresh frozen plasma packs produced by apheresis. The aim of this study was to investigate anaphylatoxin generation during apheresis production in relation to two frequently used techniques: employing either centrifugation alone or centrifugation with simultaneous filtration. The concentrations of C3a. C5a and sC5b-9 were measured in 50 plasmas after apheresis and before freezing generated by combined centrifugation and filtration and in 50 plasmas generated solely by centrifugation and in the corresponding 100 donors before apheresis. The median C3a concentration increased during apheresis by centrifugation alone from 62 (donor) to 380 micrograms L-1 (FFP pack) and during apheresis by combined centrifugation and filtration from 70 to 992 micrograms L-1. The median C5a concentration increased during apheresis by centrifugation alone from 0.38 to 0.83 microgram L-1 and during apheresis by combined centrifugation and filtration from 0.29 to 4.9 micrograms L-1. The soluble terminal complement complex increased only by combined centrifugation and filtration apheresis from 162 to 426 micrograms L-1. Complement activation during apheresis by combined centrifugation and filtration is more pronounced than that obtained by the centrifugation method alone. Changes in the construction or the materials used in the membrane-type separation units may reveal possibilities of prevention.

Assessment of complement activation during membrane‐based plasmapheresis procedures

“…Auto-C used more mean anticoagulant (124 ml) than FC (112 ml) but the anticoagulant/plasma volume ratio was similar in each group (0.17-0.18) and analysis of individual plasma samples data from each group (not shown) failed to reveal an influence of anticoagulant volume or blood volume processed on complement activation. In addition, our work appears largely consistent with previous data [4,5], and when we compare the Auto-C data with those obtained following exactly the same study design with Haemonetics Rev F, Rev G, and HSC (Table III) [6], we find much higher mean C3a/C3a des Arg content from the combined centrifugation and filtration method than in the centrifugation procedures. Possibly, apheresis procedure design and/or the device chemistry, as detailed in Table IV, have an impact on complement activation, especially C3a/C3a des Arg content.…”

“…The production of anaphylatoxins may also derive from activation by other enzymes, like plasmin and kallikrein, which may directly cleave C3, C4, and C5. Two studies suggest C3a and C5a generation during a procedure that separates blood cells from plasma by a combined centrifugation and membrane filtration method, whereas essentially no activation occurs with centrifugation only [4,5]. In an earlier study [6], we did not find C3 and C5 activation in plasma from 3 centrifugal Haemonetics PCS Ò 2 apheresis procedures, Revision F (Rev F), Rev G, and high separation core (HSC) [6].…”

“…Respective mean levels in recovered plasma donations were 320 and 390 ng/ml, and 0.8 and 0.9 ng/ml, respectively. C3 and C5 activation was subsequently found higher in procedures that separate plasma by centrifugation combined with filtration (identified in Sonntag et al [5], as CFM, and described as a separation unit for simultaneous centrifugation at 5,650-7,000 rpm and filtration across a nylon membrane with a surface area of 60 cm 2 and a pore size of 0.7 lm [5]) than by centrifugation only (CM) [5]. The median C3a/ C3a des Arg content was 380 ng/ml in CM plasma and 992 ng/ml in CFM plasma, and median C5a/C5a des Arg content was 0.83 and 4.9 ng/ml, respectively.…”

Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem/progenitor cells, and C3a enhances their homing-related responses to SDF-1

“…51,52 The mechanisms underlying this phenomenon have, however, not yet been elucidated, although several have been proposed. 22,33,53,54 Because the complement system is activated during mobilization and leukapheresis, 55 mobilized stem/progenitor cells are exposed to C3a anaphylatoxin, whose priming effect could increase their homing after transplantation. In fact, we observed in these studies that murine Sca-1 ϩ BM MNCs primed by C3a before transplantation engrafted faster.…”

Complement activation by in vivo neonatal and in vitro extracorporeal membrane oxygenation

“…Complement activation has also been described during cardiopulmonary bypass and the apheresis technique. [10][11][12] In contrast to cardiopulmonary bypass, which lasts only for a few hours and is combined with deep hypothermia, ECMO lasts for several days, is performed at normal temperature and the patient sometimes has systemic infection.…”