Adsorption of Anaphylatoxins and Platelet-Specific Proteins by Filtration of Platelet Concentrates with a Polyester Leukocyte Reduction Filter

Abstract

Anaphylatoxins generated during storage of platelet concentrates (PCs) may potentially have side effects on platelet transfusion. We evaluated the anaphy- latoxin-scavenging abilities of white blood cell reduction filters. Among the commercially available filters for PCs, one made with polyester fiber (PL50) dramatically adsorbed C3a and C4a anaphylatoxins to the respective mean level of 1,721-208 ng/ml and 1,240-141 ng/ml in 3-day-old PCs. C3a and C4a were measured as the native and des Arg form of each complement by radioimmunoassay. C3a and C4a anaphylatoxins in the supernatant plasma fraction from 3-day-old PC again decreased from 1,136 to 114 ng/ml and from 1,086 to 65 ng/ml, respectively. The filter also adsorbed 85% of platelet factor 4 (PF4) and 31% of β-thromboglobulin (β-TG), which had been released from platelets into the plasma during storage. The plasma levels of adhesive proteins such as fibronectin, fibrinogen, and von Willebrand factor, and plasma lactate dehydrogenase activity did not decrease after filtration. Another polyester filter (PL5A), on the other hand, significantly increased C3a and C4a levels with filtration. In addition, there was no PF4 adsorption ability during the filtration. The filters for red cells (RC50, BPF4, and R500A) had no anaphyla- toxin adsorption capabilities. The observed specific adsorption of anaphylatoxins might be attributed to the electrostatic force between the positively charged anaphylatoxins with high pi and the possibly negatively charged filter membranes. Since PF4 and ß-TG have positively charged moieties in the C-terminal position, the same adsorption mechanism might operate. We have obtained a useful scavenging filter for the evaluation of side effects of anaphylatoxins on patients who received old PCs.

Filtration of methylene blue‐photooxidized plasma: influence on coagulation and cellular contamination

“…As previously described for some filters, PF4 was reduced after filtration through the MBF2 and the MBF3 3,22 . This adsorption phenomenon has been attributed to the electrostatic force between the positively charged part of the measured factors and the negatively charged filter membrane 22 .…”

Evaluation of pooled platelet concentrates using prestorage versus poststorage WBC reduction: impact of filtration timing

“…Third, our study confirms and extends previous work showing a storage‐promoted accumulation in the PCs of bioreactive substances (IL‐6, IL‐8, TGFβ1, C3a, and C4a). The concentrations of these substances in our non‐WBC‐reduced PCs after 5 days of storage were either close to (TGFβ1), lower than (IL‐8, IL‐6, and TNFα), or higher than (C3a and C4a) those reported by other studies 8,12,14–16,27 . Several factors could contribute to interstudy differences in the poststorage content of bioreactive product in PCs, including the method for preparation of units, their platelet and WBC contents, and the type of storage containers.…”

“…Although other substances, such as IL‐1 and C5a, may also be involved in transfusion reactions, previous reports have shown less accumulation of these compounds in PCs than was found for those measured in the present study 5,6,14,16 …”

“…Other proposed benefits of performing WBC reduction in a laboratory setting are superior standardization and quality control of the filtration procedure, as compared to those achievable with bedside filtration 11 . Nevertheless, bedside filtration of PCs is still widely used in clinical transfusion practice, probably for economic and logistic reasons 11 and because trials have shown that some bioactive substances potentially implicated in FNHTRs might be removed by bedside filters 12–14 …”

“…In addition, we have investigated the accumulation in PCs of two anaphylatoxins with proinflammatory activity, C3a and C4a. Despite the fact that there is no definitive clinical evidence that passive infusion of C3 and C4 fragments is associated with FNHTRs, it has been suggested that these activated complement fragments may contribute to such reactions by increasing the production of cytokines by monocytes 14,16 . Moreover, measurement of C3a and C4a levels may help to evaluate the activation status of the alternative and classic (C4a) pathways of the complement cascade during storage of PCs and to clarify the role of WBCs and of the filtration process in these pathways.…”