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Robert S. Poston
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Andrew Lee
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Ann Thorac Surg 2006;81:104-111
© 2006 The Society of Thoracic Surgeons

Original article: Cardiovascular

Aprotinin Shows Both Hemostatic and Antithrombotic Effects During Off-Pump Coronary Artery Bypass Grafting

Robert S. Poston, MD a , * , Charles White, MD b , Junyan Gu, MD, PhD a , James Brown, MD a , James Gammie, MD a , Richard N. Pierson, MD a , Andrew Lee a , Ingrid Connerney, RN, DrPH c , Thrity Avari, MS e , Robert Christenson, PhD d , Udaya Tandry, PhD f , Bartley P. Griffith, MD a

a Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland
b Department of Radiology, University of Maryland School of Medicine, Baltimore, Maryland
c Department of Clinical Effectiveness, University of Maryland School of Medicine, Baltimore, Maryland
d Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland
e Chronolog Corp, Havertown, Pennsylvania
f Sinai Center for Thrombosis Research, Baltimore, Maryland

Accepted for publication May 10, 2005.

* Address correspondence to Dr Poston, Division of Cardiac Surgery, N4W94 22 S Greene St, Baltimore, MD 21201 (Email: rposton{at}smail.umaryland.edu).

Presented at the Forty-first Annual Meeting of The Society of Thoracic Surgeons, Tampa, FL, Jan 24–26, 2005.

BACKGROUND: Hemostatic drugs are widely thought to be unnecessary and potentially detrimental in off-pump coronary artery bypass graft surgery (OPCABG), despite well-established use in on-pump surgery. In a randomized, prospective OPCABG trial, we assessed efficacy and safety of aprotinin through a comprehensive assessment of graft patency and hematologic function.

METHODS: Sixty patients were randomly assigned to full-dose aprotinin or placebo. Heparin was titrated to a kaolin-based activated clotting time of greater than 300 seconds. Exclusionary criteria included creatinine greater than 2 mg/dL, conversion to on-pump CABG, and preoperative GPIIb/IIIa inhibition. Hematologic assessments were obtained preoperatively, at the end of surgery, and on days 1 and 3: mean platelet volume, thrombin generation (prothrombin fragment 1.2 assay), and aspirin resistance using a modified thrombelastography, whole blood aggregometry, 11-dehydro-thromboxane B2 levels, and flow cytometry. Thrombotic events were defined as postoperative myocardial infarction by electrocardiography or elevated troponin I, clinical stroke by examination and head computed tomography, and bypass graft failure by multichannel computed tomography angiography on day 5.

RESULTS: Aprotinin was associated with a significant reduction in intraoperative and postoperative blood loss compared with placebo but had no effect on transfusion rates. Patients treated with aprotinin had significantly fewer thrombotic events (3% versus 23%, p < 0.05, Fisher's exact test) and less postoperative aspirin resistance (20% versus 46%, respectively, p < 0.05, Fisher's exact test). Postoperative prothrombin fragment 1.2 level was reduced by aprotinin use.

CONCLUSIONS: Aprotinin reduced perioperative bleeding after OPCABG. Preserved aspirin sensitivity in the aprotinin group may explain the observed reduction in thrombotic events and might be related to the suppression of perioperative and transmyocardial thrombin formation.




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