A dose-determining trial of heparinase-I (Neutralase) for heparin neutralization in coronary artery surgery.
Heparinase-I, a specific heparin-degrading enzyme, may represent an alternative to protamine. We explored the dose of heparinase-I for efficacy and safety in patients undergoing coronary artery surgery. At the conclusion of cardiopulmonary bypass, subjects received 5, 7, or 10 microg/kg of open-label heparinase-I instead of protamine. Activated clotting time (ACT) and its difference from a contemporaneous heparin-free sample (DeltaACT) at 3 min before and 3, 6, and 9 min after heparinase-I determined reversal efficacy. After surgery, we recorded hourly chest tube drainage. Systemic and pulmonary arterial blood pressure and cardiac output measurements before and immediately after heparinase-I were used to evaluate hemodynamic safety. Coagulation measurements included anti-factor Xa and anti-factor IIa activities. Forty-nine patients from seven institutions participated: 12 received 5 microg/kg, 21 received 7 microg/kg, 4 received two doses of 7 microg/kg, 8 received 10 microg/kg, and 4 received two doses of 10 microg/kg. Treatment groups did not differ demographically. Median DeltaACT 9 min later was 11, 7, and 4 s for the 5, 7, and 10 microg/kg groups, respectively. No adverse hemodynamic changes occurred with heparinase-I administration. The authors conclude that heparinase-I effectively restored the ACT after cardiopulmonary bypass. This effect appeared to be dose dependent.


CONCLUSIONS
Heparinase-I (Neutralase(TM)) successfully restored activated coagulation time with no adverse hemodynamic events in patients undergoing coronary artery surgery with cardiopulmonary bypass in an open-label dose-determining trial.
Heres
E K
EK
Allegheny General Hospital, Pittsburgh, Pennsylvania, USA.
Horrow
J C
JC
Gravlee
G P
GP
Tardiff
B E
BE
Luber
J
J
Schneider
J
J
Barragry
T
T
Broughton
R
R
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D015505:Chest Tubes; D001026:Coronary Artery Bypass; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006494:Heparin Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D019763:Heparin Lyase / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011479:Protamines / Q000494:pharmacology; D014914:Whole Blood Coagulation Time
D000925:Anticoagulants; D006494:Heparin Antagonists; D011479:Protamines; D006493:Heparin; D019763:Heparin Lyase