Aprotinin

Aprotinin is a polypeptide extracted from bovine lung and composed of 58 amino acids with a molecular weight of 6’512 Daltons.
Aprotinin is a polyvalent reversible inhibitor of serine proteinases including plasmin and kallikrein. The active loop contains the reactive lysine residue in position 15, the tertiary structure shows a pear-shaped unit which fits exactly into the binding site of serine proteinases.

Pharmacological activity

Aprotinin slows down fibrinolysis, the process that leads to the breakdown of blood clots. In addition to its anti-fibrinolytic activity, aprotinin is also thought to preserve platelet function and have anti-inflammatory effects, both of which may be mediated by inhibition of protease-activated receptors expressed on platelets, vascular endothelium, and neutrophils.

Main therapeutic applications

  • Use in cardiac surgery:
    Aprotinin is indicated for prophylactic use to reduce blood loss and blood transfusion in adult patients who are at high risk of major bleeding. In a finished dosage form, Aprotinin is used to reduce perioperative blood loss and transfusion requirements in patients during and following cardiopulmonary bypass (CPB) in the course of coronary artery bypass graft surgery. The effects of Aprotinin use in CPB involves a reduction in inflammatory response, through its inhibition of multiple mediators, which translates into a decreased need for allogeneic blood transfusions, reduced bleeding, and decreased mediastinal re-exploration for bleeding.
  • Use in Fibrin sealant:
    Aprotinin is added to fibrin glue to delay the fibrinolytic action of plasmin and to stabilize the  fibrinogen and thrombin components.
  • Use in biopharmaceutical processes:
    Aprotinin can be used for the isolation of proteins as well as for biopharmaceutical downstream purification to prevent protein degradation during lysis or homogenizaton of cells and tissues: it inhibits undesired proteolytic activity of serine proteases such as trypsin, plasmin, trypsinogen, urokinase, chymotrypsin, kallikrein, elastase and others.

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