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Medline ® Abstract for Reference 66

of 'Antithrombin deficiency'

66
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Recombinant human antithrombin III restores heparin responsiveness and decreases activation of coagulation in heparin-resistant patients during cardiopulmonary bypass.
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Avidan MS, Levy JH, van Aken H, Feneck RO, Latimer RD, Ott E, Martin E, Birnbaum DE, Bonfiglio LJ, Kajdasz DK, Despotis GJ
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J Thorac Cardiovasc Surg. 2005 Jul;130(1):107-13.
 
OBJECTIVES: 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.
CONCLUSION: 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.
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Department of Anesthesiology and Cardiothoracic Surgery, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA. avidanm@msnotes.wustl.edu
PMID