Pharmacological approaches to reducing allogeneic blood exposure

This article discusses evidence for the role of pharmacological interventions such as the protease inhibitor aprotinin (Trasylol(R)), lysine analogue anti-fibrinolytics [tranexamic acid (Cyclokapron(R)) and epsilon aminocaproic acid (Amicar(R))], DDAVP (Desmopressin(R)) and recombinant Factor VIIa (NovoSeven(R)), in preventing the need for blood and blood-component therapies after major (cardiac, hepatic and orthopaedic/trauma) surgery. The data show that aprotinin is consistently effective in reducing globally the transfusion burden in cardiac and hepatic surgical procedures. However, there are little data to support its use in routine elective orthopaedic surgery. Multiple studies have failed to show an increased risk for myocardial ischaemia or infarction with aprotinin, and there may even be a reduced incidence of perioperative stroke in patients undergoing cardiac surgery. An increased probability of a hypersensitivity reaction when the drug is readministered within a 6-month period remains a significant issue. The data for the lysine analogue anti-fibrinolytics show no evidence of efficacy in reducing the transfusion burden for epsilon aminocaproic acid and inconsistent results with tranexamic acid in cardiac and hepatic surgery. As with aprotinin therapy, there is a paucity of data to support their use in routine elective orthopaedic surgery. There are no data to support the routine use of DDAVP to reduce the transfusion burden. Limited data suggest that this drug may be effective when a defect in platelet function is demonstrated. This aspect deserves further investigation. Recombinant activated Factor VII (rFVIIa) has proven benefit for its licensed indication to reduce bleeding in haemophiliacs with inhibitors to Factors VIII and IX. Reports of benefit in other instances are largely anecdotal. Hence, at this time it is therefore speculative and premature to suggest whether there is a place for this agent in routine clinical practice. No adequately powered, placebo-controlled prospective studies are available to investigate the safety of the lysine analogues, DDAVP or rFVIIa in cardiac, hepatic or orthopaedic surgery.