Aprotinin

In plain language

Aprotinin is a 58-amino-acid protein from cow lungs, famous and infamous, that was used for decades to cut bleeding during heart surgery. It was sold as Trasylol.

It blocks the enzymes that dissolve clots and digest proteins, so surgeons could operate with less blood loss. In 2008 it was pulled from the market after studies suggested kidney failure and deaths, a decision still debated, because the strongest randomized evidence was mixed. Canada and Europe later restored restricted use.

For students

Aprotinin is a 58-residue Kunitz-type serine protease inhibitor (about 6,511 Da), essentially bovine pancreatic trypsin inhibitor, homologous to the leech anticoagulant eglin family in function if not sequence. It inhibits trypsin, chymotrypsin, kallikrein and plasmin at nanomolar potency, the last effect reducing fibrinolysis and blood loss during cardiopulmonary bypass.

Marketed from the 1960s and FDA-approved for coronary artery bypass grafting in 1993, observational studies (Mangano 2006 NEJM; the 2007 BART trial was halted early for mortality signal) triggered withdrawal in 2007-2008. Subsequent reanalysis and European review (2016 SAGE/EMA decision restoring restricted use under risk management) reopened the debate: the drug remains available in Canada and the EU for high-bleeding-risk CABG, while no U.S. product is marketed. It is also a laboratory reagent and a classic Kunitz-domain teaching molecule.

For researchers and instructors

Biochemistry. The Kunitz domain (one of the most-studied protein folds, aprotinin is a named reference structure in folding kinetics) is the core lesson; ecallantide and the eglin C family are its pharmacological descendants.

Pharmacology. Half-life about 150 minutes; high-dose regimen (about 280 mg loading plus infusion); principal risks are renal dysfunction and, in context of observational data, mortality signal; hypersensitivity on re-exposure within 6 months is a contraindication.

Human evidence. Phase 3 trials showed 40% reductions in blood loss and transfusion; the Mangano observational study (n=4,374) and early-stopped BART randomized trial (n=2,035) drove withdrawal; EMA's 2016 review concluded restricted benefit-risk, a textbook case of conflicting evidence hierarchies.

Teaching point. The definitive case study in observational-versus-randomized evidence conflict, publication-driven regulatory reversal, and the complexity of drug safety signals in surgery.