title: A phase III, double-blind, placebo-controlled, multicenter study on the efficacy of recombinant human antithrombin in heparin-resistant patients scheduled to undergo cardiac surgery necessitating cardiopulmonary bypass.
abstract: BACKGROUND
  The study evaluated the efficacy of recombinant human antithrombin (rhAT) for restoring heparin responsiveness in heparin resistant patients undergoing cardiac surgery.
  
  
  METHODS
  This was a multicenter, randomized, double-blind, placebo-controlled study in heparin-resistant patients undergoing cardiac surgery with cardiopulmonary bypass. Heparin resistance was diagnosed when the activated clotting time was less than 480 s after 400 U/kg heparin. Fifty-four heparin-resistant patients were randomized. One cohort received 75 U/kg rhAT, and the other received normal saline. If the activated clotting time remained less than 480 s, this was considered treatment failure, and 2 units fresh frozen plasma was transfused. Patients were monitored for adverse events.
  
  
  RESULTS
  Only 19% of patients in the rhAT group received fresh frozen plasma, compared with 81% of patients in the placebo group (P < 0.001). During their hospitalization, 48% of patients in the rhAT group received fresh frozen plasma, compared with 85% of patients in the placebo group (P = 0.009). Patients in the placebo group required higher heparin doses (P < 0.005) for anticoagulation. There was no increase in serious adverse events associated with rhAT. There was increased blood loss 12 h postoperatively (P = 0.05) with a trend toward increased 24-h bleeding in the rhAT group (P = 0.06). There was no difference between the groups in blood and platelet transfusions.
  
  
  CONCLUSIONS
  Treatment with 75 U/kg rhAT is effective in restoring heparin responsiveness and promoting therapeutic anticoagulation in the majority of heparin-resistant patients. Treating heparin-resistant patients with rhAT may decrease the requirement for heparin and fresh frozen plasma.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA. avidanm@msnotes.wustl.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Avidan
authors.forename: Jerrold H
authors.initials: JH
authors.lastname: Levy
authors.forename: Jens
authors.initials: J
authors.lastname: Scholz
authors.forename: Elise
authors.initials: E
authors.lastname: Delphin
authors.forename: Peter M J
authors.initials: PM
authors.lastname: Rosseel
authors.forename: Michael B
authors.initials: MB
authors.lastname: Howie
authors.forename: Irwin
authors.initials: I
authors.lastname: Gratz
authors.forename: Charles R
authors.initials: CR
authors.lastname: Bush
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Skubas
authors.forename: Gabriel S
authors.initials: GS
authors.lastname: Aldea
authors.forename: Michael
authors.initials: M
authors.lastname: Licina
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bonfiglio
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Kajdasz
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ott
authors.forename: George J
authors.initials: GJ
authors.lastname: Despotis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002315:Cardiopulmonary Bypass / Q000379:methods / Q000706:statistics & numerical data*; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D006493:Heparin