Aprotinin.

OBJECTIVE

To review the clinical pharmacology of aprotinin in patients undergoing surgical procedures involving major blood loss, namely, coronary artery bypass graft (CABG).

DATA SOURCES: A MEDLINE search was used to identify French- and English-language publications on aprotinin using the indexing terms aprotinin, cardiothoracic surgery, and hemorrhage. The MEDLINE search was supplemented by review of article bibliographies. Data also were obtained from the approved Canadian and US product labels.

STUDY SELECTIONS: All abstracts and uncontrolled and controlled clinical trials were reviewed.

DATA EXTRACTION: Study design, population, results, and safety information were retained. Efficacy conclusions were drawn from controlled trials.

DATA SYNTHESIS: Aprotinin, a serine protease inhibitor isolated from bovine lung tissue, decreases bleeding after cardiac surgery by mechanisms including antifibrinolytic activity and preservation of platelet function. Several trials have shown that aprotinin reduced blood loss and transfusion requirements in patients undergoing CABG. Its use in other surgical procedures involving major blood loss has been reported. Aprotinin is well tolerated, with minor allergic reactions being the most frequently reported adverse effect. Although unsubstantiated, the possibility that aprotinin could create a prothrombic state leading to early graft occlusion and formation of microthrombi in renal and coronary vasculatures is of concern.

CONCLUSIONS

Aprotinin is an effective hemostatic agent in CABG. Clear definitions of indications, dosing, safety, and repeated use remain to be investigated thoroughly.