Anticoagulation-dependent inhibition of in vitro complement activation by anti-apo-B sepharose 4B CL.
During LDL apheresis, various combinations of heparin and citrate are used for anticoagulation. With an in vitro batch system we examined whether heparin/citrate combinations can be optimized in terms of complement activation inhibition without the loss of anticoagulant potency. Plasma anticoagulated by using six clinically applicable regimens was incubated with anti-apo-B antibody-coupled Sepharose 4B CL, and the anaphylatoxin content of the supernatant was investigated. A significant dose-dependent reduction of complement activation was achieved by anticoagulating whole blood with 10 U/ml heparin (p < 0.05) if compared with serum whereas citrate inhibited more effectively the generation of C5a (desarg) even at a low concentration (ACD-B 1:20) (p < 0.01). The lowest anaphylatoxin level was generated when heparin (10 U/ml) plus citrate (ACD-B 1:10) were applied, although such an approach may be of limited clinical interest. The empirically chosen heparin plus citrate ratio (2 U/ml, 1:20, respectively) provides for an optimal and almost ideal inhibition of complement activation and contributes considerably to the good tolerability of the immunoadsorbent.
Kadar
J G
JG
Hämapherese Einheit, Klinik I für Innere Medizin, Universität zu Köln.
Parusel
M
M
Borberg
H
H
D001055:Apolipoproteins B / Q000097:blood*; D001781:Blood Component Removal; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid; D003167:Complement Activation / Q000187:drug effects*; D015926:Complement C3a / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D015934:Complement C4a / Q000037:antagonists & inhibitors; D015937:Complement C5a, des-Arginine / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000494:pharmacology*; D006801:Humans
D001055:Apolipoproteins B; D002951:Citrates; D015937:Complement C5a, des-Arginine; C044541:complement C3a, des-Arg-(77)-; C051066:complement C4a, des-Arg; D019343:Citric Acid; D015926:Complement C3a; D015934:Complement C4a; D006493:Heparin