Recombinant human antithrombin III restores heparin responsiveness and decreases activation of coagulation in heparin-resistant patients during cardiopulmonary bypass.
OBJECTIVE
We sought to evaluate the efficacy of recombinant human antithrombin III for restoration of heparin responsiveness in heparin-resistant patients scheduled for cardiac surgery.


METHODS
This was a multicenter, randomized, double-blind, placebo-controlled study in heparin-resistant patients undergoing elective cardiac surgery. Patients were considered heparin resistant if the activated clotting time was less than 480 seconds after 400 U/kg heparin. Fifty-two heparin-resistant patients were randomized into 2 cohorts. One cohort received a single bolus (75 U/kg) of recombinant human antithrombin III (n = 28), and the other, the placebo group (n = 24), received a normal saline bolus. If the activated clotting time remained less than 480 seconds, this was defined as treatment failure, and 2 units of fresh frozen plasma were transfused. Patients were monitored for adverse events during hospitalization.


RESULTS
Six (21%) of the patients in the recombinant human antithrombin III group received fresh frozen plasma transfusions compared with 22 (92%) of the placebo-treated patients ( P < .001). Two units of fresh frozen plasma did not restore heparin responsiveness. There was no increased incidence of adverse events associated with recombinant human antithrombin III administration. Postoperative 24-hour chest tube bleeding was not different in the 2 groups. Surrogate measures of hemostatic activation suggested that there was less activation of the hemostatic system during cardiopulmonary bypass in the recombinant human antithrombin III group.


CONCLUSIONS
Treatment with recombinant human antithrombin III in a dose of 75 U/kg is effective in restoring heparin responsiveness and promoting therapeutic anticoagulation for cardiopulmonary bypass in the majority of heparin-resistant patients. Two units of fresh frozen plasma were insufficient to restore heparin responsiveness. There was no apparent increase in bleeding associated with recombinant human antithrombin III.
Avidan
M S
MS
Department of Anesthesiology and Cardiothoracic Surgery, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA. avidanm@msnotes.wustl.edu
Levy
J H
JH
van Aken
H
H
Feneck
R O
RO
Latimer
R D
RD
Ott
E
E
Martin
E
E
Birnbaum
D E
DE
Bonfiglio
L J
LJ
Kajdasz
D K
DK
Despotis
G J
GJ
D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000502:physiology; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D004351:Drug Resistance; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006488:Hemostasis, Surgical; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D014914:Whole Blood Coagulation Time
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D006493:Heparin; D010447:Peptide Hydrolases