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.
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.
Avidan
Michael S
MS
Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA. avidanm@msnotes.wustl.edu
Levy
Jerrold H
JH
Scholz
Jens
J
Delphin
Elise
E
Rosseel
Peter M J
PM
Howie
Michael B
MB
Gratz
Irwin
I
Bush
Charles R
CR
Skubas
Nikolaos
N
Aldea
Gabriel S
GS
Licina
Michael
M
Bonfiglio
Laura J
LJ
Kajdasz
Daniel K
DK
Ott
Elizabeth
E
Despotis
George J
GJ
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
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D006493:Heparin