Citrate confers less filter-induced complement activation and neutrophil degranulation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients.
BACKGROUND
During continuous venovenous haemofiltration (CVVH), regional anticoagulation with citrate may be superior to heparin in terms of biocompatibility, since heparin as opposed to citrate may activate complement (reflected by circulating C5a) and induce neutrophil degranulation in the filter and myeloperoxidase (MPO) release from endothelium.


METHODS
No anticoagulation (n = 13), unfractionated heparin (n = 8) and trisodium citrate (n = 17) regimens during CVVH were compared. Blood samples were collected pre- and postfilter; C5a, elastase and MPO were determined by ELISA. Additionally, C5a was also measured in the ultrafiltrate.


RESULTS
In the heparin group, there was C5a production across the filter which most decreased over time as compared to other groups (P = 0.007). There was also net production of elastase and MPO across the filter during heparin anticoagulation (P = 0.049 or lower), while production was minimal and absent in the no anticoagulation and citrate group, respectively. During heparin anticoagulation, plasma concentrations of MPO at the inlet increased in the first 10 minutes of CVVH (P = 0.024).


CONCLUSIONS
Citrate confers less filter-induced, potentially harmful complement activation and neutrophil degranulation and less endothelial activation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients.
Louise
L
Schilder
S Azam
SA
Nurmohamed
Pieter M
PM
ter Wee
Nanne J
NJ
Paauw
Armand R J
AR
Girbes
Albertus
A
Beishuizen
Robert H J
RH
Beelen
Department of Intensive Care, Erasmus Medical Center, Rotterdam, The Netherlands. a.b.j.groeneveld@erasmusmc.nl.
A B Johan
AB
Groeneveld
D000328:Adult; D000368:Aged; D000925:Anticoagulants; D019343:Citric Acid / Q000627:therapeutic use*; D015936:Complement C5a / Q000302:isolation & purification*; D003422:Critical Care / Q000379:methods; D016638:Critical Illness; D004357:Drug Synergism; D005260:Female; D006440:Hemofiltration / Q000009:adverse effects* / Q000379:methods; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology*; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000097:blood* / Q000473:pathology / Q000517:prevention & control*
D000925:Anticoagulants; D019343:Citric Acid; D015936:Complement C5a; D006493:Heparin