| Drug Name: |
Aprotinin |
| Applications: |
For prophylactic use to reduce perioperative blood loss and the need for blood transfusion in patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft surgery who are at an increased risk for blood loss and blood transfusion. |
| Examples of Clinical Use: |
Undergoing cardiopulmonary bypass in the course of coronary artery bypass graft surgery |
| Pharmacodynamics: |
The product is a broad spectrum protease inhibitor which modulates the systemic inflammatory response (SIR) associated with cardiopulmonary bypass (CPB) surgery. SIR results in the interrelated activation of the hemostatic, fibrinolytic, cellular and humoral inflammatory systems. The product, through its inhibition of multiple mediators [e.g., kallikrein, plasmin] results in the attenuation of inflammatory responses, fibrinolysis, and thrombin generation. The product inhibits pro-inflammatory cytokine release and maintains glycoprotein homeostasis. In platelets, the product reduces glycoprotein loss (e.g., GpIb, GpIIb/IIIa), while in granulocytes it prevents the expression of pro-inflammatory adhesive glycoproteins (e.g., CD11b). The effects of the product use in CPB involves a reduction in inflammatory response which translates into a decreased need for allogeneic blood transfusions, reduced bleeding, and decreased mediastinal re-exploration for bleeding. |
| Mechanism of action: |
Aprotinin inhibits several serine proteases, specifically trypsin, chymotrypsin and plasmin at a concentration of about 125,000 IU/ml, and kallikrein at 300,000 IU/ml. Its action on kallikrein leads to the inhibition of the formation of factor XIIa. As a result, both the intrinsic pathway of coagulation and fibrinolysis are inhibited. Its action on plasmin independently slows fibrinolysis. |
| Affected organisms: |
Humans and other mammals |
| Targets: |
Target 1. Trypsin-1; Target 2. Chymotrypsinogen B; Target 3. Plasminogen; Target 4. Kallikrein-1 |
