Aprotinin

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Abstract
Cardiopulmonary bypass (CPB) is associated with defective haemostasis which results in bleeding and the requirement for allogenic blood product transfusions in many patients undergoing open heart surgery (OHS) and/or coronary artery bypass graft surgery (CABG) with CPB. Conservation of blood has become a priority during surgery because of shortages of donor blood, the risks associated with the use of allogenic blood products and the costs of these products. Aprotinin is a serine protease inhibitor isolated from bovine lung tissue which acts in a number of interrelated ways to provide an antifibrinolytic effect, inhibit contact activation, reduce platelet dysfunction and attenuate the inflammatory response to CPB. It is used to reduce blood loss and transfusion requirements in patients with a risk of haemorrhage and has clear advantages over placebo or no treatment. High dose aprotinin significantly reduces postoperative blood loss compared with aminocaproic acid and desmopressin, and decreases transfusion requirements compared with desmopressin. Results are less consistent with tranexamic acid: high dose aprotinin either reduces blood loss significantly more than, or to an equivalent level to, tranexamic acid. A variety of other lower aprotinin dosage regimens consistently result in similar reductions in blood loss to aminocaproic acid or tranexamic acid. Data from clinical trials indicate that aprotinin is generally well tolerated, and the adverse events seen are those expected in patients undergoing OHS and/or CABG with CPB. Hypersensitivity reactions occur in 131I-labelled aprotinin was measured in the urine of healthy volunteers within 48 hours of administration. Aprotinin clearance was substantially reduced, and the elimination half-life and area under the plasma concentration-time curve increased in 2 patients with chronic renal impairment who received 140mg by intravenous infusion over 30 minutes. However, renal impairment did not affect peak plasma aprotinin concentrations or distribution half-life. The clinical efficacy of aprotinin has been evaluated in patients undergoing open heart surgery (OHS) and/or coronary artery bypass graft surgery (CABG), including those undergoing repeat sternotomy and those receiving aspirin. It has been compared with untreated controls and placebo as well as the lysine analogues tranexamic acid and aminocaproic acid, and the vasopressin analogue desmopressin. An evaluation of comparative efficacy is difficult because dosage regimens of all active treatments vary between studies. However, high dose aprotinin (see Dosage and Administration summary) significantly reduces postoperative blood loss compared with aminocaproic acid and desmopressin, and decreases transfusion requirements compared with desmopressin. Results are less consistent in comparisons with tranexamic acid: high dose aprotinin reduced blood loss significantly more than tranexamic acid in some studies and to equivalent levels in others. A variety of other lower dose aprotinin regimens consistently result in similar reductions in blood loss to aminocaproic acid...