Aminocaproic Acid

Monitoring parameters serum creatinine, blood urea nitrogen, creatine phosphokinase, and coagulation tests.[7]

Multiple methods are possible to assess fibrinolysis; however, there is no “gold standard” test. Point-of-care testing with whole blood is beneficial in the perioperative setting as it evaluates plasma and cellular contents. The most widely utilized tools for assessing fibrinolysis in the perioperative setting are thromboelastography (TEG), which uses several activators to measure viscoelastic changes in whole blood.[10]

Aminocaproic acid is of low acute toxicity. Research has found no fetal abnormalities in teratogenic in-vitro studies given aminocaproic acid doses up to 5000 mcg/kg/day. Retinal changes have been reports in dogs after receiving aminocaproic acid by mouth over one year in doses approximately seven-fold higher than the maximum recommended in-vivo dose.[6]

A significant concern is whether treatment with aminocaproic acid predisposes patients to thrombosis and intravascular coagulation. There are isolated reports of arterial or venous thrombosis, but there is underlying thrombotic comorbidity present in each case.[6]

There is no available antidote for use in the setting of aminocaproic acid toxicity. There are case reports that have described the use of tissue plasminogen activator for suspected antifibrinolytic-induced intraoperative thromboembolic events.[11]

Fibrinolysis serves as a physiologic component of hemostasis functioning to limit clot formation. The critical event for clot formation is fibrin formation following vascular injury, tissue factor binding to factor VIIa, and activation of the X-ase complex for hemostatic activation and thrombin generation. Thrombin stimulates the endothelial release of tissue plasminogen activator and increases vascular flow, kinins, and other factors that will release tissue plasminogen activator. Plasmin release follows the formation of a plasminogen-tissue plasminogen activator complex that assembles on fibrin and binds to lysine sites on fibrin clot. Once assembled, tissue plasminogen activator cleaves plasminogen to its active form plasmin. Other mechanisms can also generate plasmin, including urokinase, contact activation, and kallikrein mediated protease activation. Fibrinolysis is inhibited by plasminogen activator inhibitors (plasminogen activator inhibitor 1 and 2) and by thrombin binding to thrombomodulin to release and activate thrombin-activatable fibrinolysis inhibitor.[10] [Level 5]

After tissue injury associated with trauma and surgery, ischemia and reperfusion, or blood interaction with large nonendothelial surfaces, excessive fibrinolysis may contribute to bleeding, coagulopathies, and inflammatory responses. As a result, growing data have reported the efficacy of antifibrinolytic agents to reduce bleeding, blood transfusions, and adverse clinical outcomes. Aminocaproic acid, an antifibrinolytic agent, is one of the medications used to treat acute bleeding disorders.[10] [Level 5]

Managing life-threatening hemorrhagic events requires an interprofessional team of healthcare professionals that includes a nurse, laboratory technologists, pharmacists, and several physicians in different specialties. Without proper management, the morbidity and mortality from massive bleeding are high. It has inevitable consequences in the perioperative period, including re-operation, increased transfusion requirements, and multiorgan dysfunction.[2] [Level 1]

Prophylactic use of the synthetic lysine-analog antifibrinolytic agent, aminocaproic acid, has been the primary pharmacologic approach to blood conservation in cardiac surgery since the removal of aprotinin from clinical use.[12] [Level 1] In the 2011 Update to The Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Blood Conservation Clinical Practice Guidelines, antifibrinolytic agents were a strong recommendation as a part of the blood conservation approach.[13] [Level 5] Aminocaproic acid reduces bleeding and chest tube drainage output in cardiac surgical patients and is associated with a well-tolerated side effect profile.