Blood substitution and complement activation

Abstract

Complement activation was studied in 45 patients undergoing total hip arthroplasty under epidural anesthesia. The patients were randomly allocated to three groups. In Group I blood loss was replaced with microaggregate-poor erythrocyte concentrate (SAGM-ERC) plus 3% dextran-60 as plasma substitute, and postoperative analgesia was maintained with intramuscular ketobemidone. In Group II blood loss was replaced as in Group I, but epidural anesthesia was prolonged 12 h postoperatively and kept at a level of T4 with 0.5% bupivacaine. In Group III blood loss was replaced with non-frozen stored plasma plus SAGM-ERC, and postoperative analgesia was maintained with ketobemidone as in Group I. All groups received pre- and postoperative thrombo-prophylaxis with dextran. The plasma concentration of C3a-des-arginine (C3a-desArg) was measured by radioimmunoassay preoperatively, immediately after operation and 3, 6 and 18 h postoperatively. No significant differences in plasma C3 and C4 were found between the groups. C3a-desArg was significantly (P less than 0.01) increased up to 6 h postoperatively in Group III compared with both the preoperative value and Groups I and II. It is demonstrated that infusion of plasma can enhance or initiate endogenous complement activation. Blood component therapy with SAGM-ERC and 3% dextran-60, on the other hand, did not significantly increase the plasma level of C3a-desArg irrespective of the type of postoperative analgesia.

Complement activation during plasma production depends on the apheresis technique

“…The harmful effects of anaphylatoxin infusion on pulmonary function and granulocyte numbers and function were shown in various animal experiments (Hoffmann et al ., 1988; Watson et al ., 1988; Johnson et al ., 1996). Similar observations were reported after treatment of human patients with plasma and platelet concentrates with high anaphylatoxin content (Schött et al ., 1987; Holme et al ., 1992). The slow infusion rates used during plasma infusion may prevent harmful effects of anaphylatoxins by their short half‐life and concomitant degradation (Weisdorf et al ., 1981).…”

“…*P values less than 0ؒ01 obtained by Mann-Whitney U-test between separation techniques. †P values less than 0ؒ01 obtained by Friedman variance analysis test between concentrations during apheresis plasma production , 1987;Holme et al, 1992). The slow infusion rates used during plasma infusion may prevent harmful effects of anaphylatoxins by their short half-life and concomitant degradation (Weisdorf et al, 1981).…”

Complement activation products in liquid stored plasma and C3a kinetics after transfusion of autologous plasma

“…As standard, zymosan‐activated serum was calibrated against a solution of purified C3a‐ desArg , and the values were given as ng/ml. In contrast, in the autologous plasma samples for the infusion experiments, measurement of the levels C3a/C3a‐ desArg was taken using RIA method as previously described [32]. Thus, the measurements of C3a‐ desArg were carried out by two different methods without the possibility to parallel analysis.…”

“…Complement activation has been noted to occur in whole blood plasma [19–21], in apheresis plasma [22–25] and also during apheresis for therapeutic purposes [26–30]. Complement activation has also been described as a consequence of homologous and autologous transfusion [31, 32]. Pooled pathogen‐inactivated plasma components also have been shown to have increased levels of activated complement [33–35].…”

“…Clinical consequences of the infusion of complement activation products have been suggested to be either an immunosuppressive effect [27] or adverse reactions [32, 36, 37]. Activated complement factors may further induce or sustain activation of the complement as well as the coagulation and contact activation systems [38].…”