Lessons from the aprotinin saga: current perspective on antifibrinolytic therapy in cardiac surgery.
Antifibrinolytic agents have been prophylactically administered to patients undergoing cardiopulmonary bypass (CPB) to reduce postoperative bleeding due to plasmin-mediated coagulation disturbances. After the recent market withdrawal of aprotinin, a potent bovine-derived plasmin inhibitor, two lysine analogs, epsilon-aminocaproic acid and tranexamic acid are currently available for clinical use. Although the use of aprotinin recently raised major concerns about postoperative thrombosis and organ dysfunctions, there is a paucity of information on the potential complications related to lysine analogs. Using the available preclinical and clinical data, we present current perspectives on the hemostatic mechanism and potential harms of antifbirnolytic therapy related to cardiac surgery. Fibrin formation is the critical step for hemostasis at the site of vascular injury, and localized fibrinolytic activity counterbalances excess fibrin formation which might result in vascular occlusion. Inhibition of the endogenous fibrinolytic system may be associated with thrombotic complications in susceptible organs. It is thus important to understand CPB-related changes in endogenous fibrinolytic proteins (e.g., tissue plasminogen activator (tPA), plasminogen) and antifibrinolytic proteins (e.g., alpha(2)-antiplasmin).
Ide
Masahiro
M
Kobe Anesthesia Associates, Hyogo, Japan.
Bolliger
Daniel
D
Taketomi
Taro
T
Tanaka
Kenichi A
KA
D015119:Aminocaproic Acid / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000933:Antifibrinolytic Agents / Q000009:adverse effects* / Q000600:supply & distribution / Q000627:therapeutic use*; D007611:Aprotinin / Q000009:adverse effects* / Q000600:supply & distribution / Q000627:therapeutic use*; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D006801:Humans; D013927:Thrombosis / Q000139:chemically induced; D014148:Tranexamic Acid / Q000009:adverse effects / Q000627:therapeutic use
D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid; D007611:Aprotinin; D015119:Aminocaproic Acid