SCAH Newsletter Archive

Aprotinin reduces bleeding and blood product use in patients treated with clopidogrel before coronary artery bypass grafting.

Gabriella Lindvall, MD; Ulrik Sartipy, MD; Janvander Linden, MD, PhD. Annals of Thoracic Surgery 2005;80:922-7

Reviewer: Mohammed M. Minhaj, MD
University of Chicago
Chicago, IL

Abstract: This study was a retrospective review of the use of aprotinin in patients who had emergent coronary artery bypass graft (CABG) surgery and had been on clopidogrel within five days of surgery. Of the 33 patients whose records were reviewed, 18 patients received full dose aprotinin regimens while 15 did not (these 15 served as the control group). Full dose aprotinin was as follows: Two million KIU before surgery, 500,000 KIU during the operation, and an additional two million KIU during cardiopulmonary bypass (CPB) as part of the CPB priming solution.

The two groups were similar with respect to base line characteristics and operative data (anesthetic/CPB management, surgical techniques employed, etc). Mean postoperative bleeding was 710 mL in the aprotinin group vs. 1210 mL in the control group (p=0.004). Additionally, the aprotinin group received significantly fewer blood transfusions, platelet transfusions, and fewer blood products overall vs. the control group. There were only three reoperations, all of which occurred in the control group. Based on these results the investigators determined that aprotinin use in patients on clopi-dogrel significantly reduces blood loss, administration of blood products and reoperations.

Comments: The use of clopidogrel (an irreversible platelet inhibitor) has risen dramatically since its introduction in the late 1990's. It has been shown to be beneficial in patients with significant coronary artery disease, especially those with unstable angina and is routinely used post percutaneous coronary interventions to prevent thrombotic events and their sequelae. Additionally, patients with peripheral vascular disease and ischemic strokes may also benefit from its use. Unfortunately, the effects of clopidogrel can last 5-10 days even after cessation of the drug, making its anti-platelet function detrimental in a perioperative setting as in emergent cases it cannot be held adequately in advance..Indeed, studies have demonstrated that patients on aspirin and clopidogrel have increased blood loss and requirements for transfusion when CABG surgery.

The use of aprotinin in cardiac surgery has been well documented to reduce blood loss and postoperative bleeding. This agent is a serine protease inhibitor with platelet preservation activity on CPB. While not without risks, rarely anaphylaxis can occur especially on repeat administration, the use of aprotinin has been recently shown to possibly decrease neurological morbidity as well as its positive effects on hemostasis.

This study demonstrated that patients exposed to clopidogrel within five days of surgery who received a full dose regimen of aprotinin were three times less likely to require blood products, had less perioperative bleeding and lower rate of reoperation. This is important for many reasons including economical (fewer operations/blood products) as well as from a resource standpoint (with the blood product shortage seen on a routine basis).

A potential drawback, which the authors addressed as well, was the nature of the study being retrospective not allowing for randomization of patients. There may have been some underlying patient characteristics (e.g. baseline platelet function) that could have altered the results. Additionally the relatively small sample size could affect results.

Overall, the study does have impressive results, even with these reservations and hopefully a prospective trial (which the authors alluded to which may be forthcoming) will serve to validate their preliminary results.

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