Pharmacologic C5-complement suppression reduces blood loss during on-pump cardiac surgery.
BACKGROUND
Inflammation contributes to morbidity following on-pump cardiac surgery. Complement activation during cardiopulmonary bypass has been associated with the postoperative bleeding and tissue injury. This study examines the pharmacology and impact on blood loss of complement C5 suppression with pexelizumab in patients undergoing cardiac surgery with cardiopulmonary bypass.


METHODS
Pexelizumab, a humanized monoclonal antibody single-chain fragment that binds to the human C5 complement component, was studied in a Phase II multicentered clinical trial. CABG (n = 800) and CABG with concomitant valve surgery (n = 114) patients were evaluated. Patients were randomized to either: pexelizumab bolus (2.0 mg/kg) + placebo infusion; pexelizumab bolus (2.0 mg/kg) + pexelizumab infusion (0.05 mg/kg/hour for 24 hours); or placebo bolus + placebo infusion. Pharmacology, chest tube drainage, and transfusion requirements were assessed.


RESULTS
Mean maximum pexelizumab serum concentration was similar for bolus and bolus + infusion-treated patients. Complement-dependent serum hemolytic activity was completely suppressed within 1 hour following pexelizumab bolus, however, suppression was maintained for a longer duration in the bolus + infusion compared to the bolus-only treated patients. A reduction in chest tube drainage was observed for all pexelizumab-treated patients, although transfusion of blood products was similar across all study groups.


CONCLUSIONS
Pexelizumab administration inhibits complement-dependent hemolytic activity and is associated with a reduction in postoperative chest tube drainage in patients undergoing cardiac surgery requiring cardiopulmonary bypass. Further, clinical studies are needed to assess the value of complement attenuation in this setting.
Chen
John C
JC
Division of Cardiothoracic Surgery, University of Hawaii School of Medicine, Department of Anatomy and Physiology, University of Hawaii, 3288 Moanalua Road, Honolulu, HI 96819, USA. Jchen@alum.mit.edu
Rollins
Scott A
SA
Shernan
Stanton K
SK
Boyce
Steven
S
Allen
Keith
K
Wallace
Arthur
A
Malloy
Kevin J
KJ
Eng
Jamie S
JS
Colman
Robert W
RW
Fitch
Jane C K
JC
D000368:Aged; D000911:Antibodies, Monoclonal / Q000097:blood / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003182:Complement C5 / Q000187:drug effects*; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D006355:Heart-Lung Machine; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D019106:Postoperative Hemorrhage / Q000188:drug therapy*; D057127:Single-Chain Antibodies
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; D057127:Single-Chain Antibodies; C402724:pexelizumab