title: Protamine requirements in cardiac surgery: effect of changes in the heparin reference standard.
abstract: OBJECTIVE
  UFH (unfractionated heparin) and protamine are integral to cardiac surgery, and inappropriate dosing can predispose to coagulopathy and hemorrhage. The FDA (Food and Drug Administration) recently has instituted changes to UFH formulation and it is not known if this has influenced its susceptibility to neutralization by protamine. Hence, the authors sought to compare 2 commercial preparations of UFH (old and new) with regard to their neutralization by protamine in patients undergoing cardiopulmonary bypass (CPB).
  
  
  METHODS
  Prospective, observational, cohort study.
  
  
  METHODS
  Tertiary care university hospital and associated research laboratory
  
  
  METHODS
  Twenty adult patients undergoing elective cardiac surgery with CPB.
  
  
  METHODS
  Blood samples were drawn preinduction, prior to, and 5 and 30 minutes following protamine, and 0 and 2 hours after ICU admission. Protamine titration assays were conducted in vitro on samples drawn prior to and following protamine administration. Anti-IIa and anti-Xa activity were assayed in all samples.
  
  
  RESULTS
  Anti-IIa and anti-Xa activity were detected ubiquitously at all time points following CPB, and there were no differences in susceptibility to protamine neutralization between the 2 groups. In vitro protamine titration studies revealed that anti-IIa was more resistant to protamine neutralization compared to anti-Xa activity.
  
  
  CONCLUSIONS
  The 'old' and 'new' formulations of UFH evaluated in this study were similar in their susceptibility to protamine neutralization. Circulating UFH is detected as early as 5 minutes after protamine administration and anti-IIa is more resistant to protamine neutralization as compared to anti-Xa activity. Further studies are required to quantify the precise dose of protamine following CPB.
authors.affiliation: Department of Anesthesia and Perioperative Medicine, Schulich School of Medicine, Western University, London, ON. Electronic address: Ravi.Taneja@lhsc.on.ca.
authors.forename: Ravi
authors.initials: R
authors.lastname: Taneja
authors.affiliation: Department of Pediatrics, McMaster University, Thrombosis and Atherosclerosis Research Institute, Hamilton, ON.
authors.forename: Leslie
authors.initials: L
authors.lastname: Berry
authors.affiliation: Department of Anesthesia and Perioperative Medicine, Schulich School of Medicine, Western University, London, ON.
authors.forename: Unnikrishnan
authors.initials: U
authors.lastname: Pappu
authors.affiliation: Department of Epidemiology and Biostatistics, Western University, London, ON.
authors.forename: Larry
authors.initials: L
authors.lastname: Stitt
authors.affiliation: George Washington University, Washington, D.C.
authors.forename: Puneet
authors.initials: P
authors.lastname: Sayal
authors.affiliation: London Health Science Center, London, ON.
authors.forename: Peter
authors.initials: P
authors.lastname: Allen
authors.affiliation: Hemostasis Reference Laboratory Inc., Hamilton, ON, Canada.
authors.forename: Hugh
authors.initials: H
authors.lastname: Hoogendoorn
authors.affiliation: Department of Pediatrics, McMaster University, Thrombosis and Atherosclerosis Research Institute, Hamilton, ON.
authors.forename: Anthony
authors.initials: A
authors.lastname: Chan
mesh_terms: D000368:Aged; D000818:Animals; D006348:Cardiac Surgical Procedures / Q000639:trends; D002626:Chemistry, Pharmaceutical; D015331:Cohort Studies; D005260:Female; D006493:Heparin / Q000097:blood / Q000592:standards* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011479:Protamines / Q000097:blood / Q000592:standards* / Q000627:therapeutic use*; D012015:Reference Standards; D013552:Swine
chemical_list: D011479:Protamines; D006493:Heparin
keywords: anti-Xa, anti-IIa; cardiopulmonary bypass; heparin, protamine