TRASYLOL

Indications

• Cardiopulmonary bypass surgery
• Reduction of bleeding during surgery
• Minimization of blood transfusion requirements

Dosage

Children: Refer to the BNF for

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Aprotinin inhibits serine proteases, including trypsin, chymotrypsin, and plasmin, at concentrations around 125,000 IU/mL, and kallikrein at 300,000 IU/mL. This inhibition prevents the formation of factor XIIa, thereby inhibiting the intrinsic coagulation pathway and fibrinolysis. By reducing plasmin activity, aprotinin slows down fibrinolysis. In addition to this, aprotinin modulates the systemic inflammatory response by inhibiting pro-inflammatory cytokine release and maintaining glycoprotein homeostasis, which preserves platelet function and reduces inflammatory responses during and after CPB.

Pharmacodynamics

Aprotinin's pharmacodynamic effects are primarily observed in its ability to modulate the systemic inflammatory response (SIR) during cardiopulmonary bypass surgery. By inhibiting multiple mediators such as kallikrein and plasmin, aprotinin decreases thrombin generation and inflammatory responses. It also reduces glycoprotein loss in platelets and prevents the expression of pro-inflammatory adhesive glycoproteins in granulocytes, leading to improved hemostasis, decreased bleeding, and reduced transfusion needs.

Pharmacokinetics

Aprotinin is administered via intravenous route, and its pharmacokinetics involve rapid distribution and elimination from the bloodstream. The drug's half-life and clearance can vary based on individual patient characteristics and the specifics of surgical procedures. It is primarily metabolized in the liver and eliminated via the kidneys. Continuous infusion may be necessary during prolonged surgical procedures to maintain effective plasma concentrations.

Contra-indications

• History of hypersensitivity to aprotinin or any of its components
• Current or recent use of other anticoagulants (e.g., heparin, warfarin) that may increase bleeding risk

Adverse effects

• Anaphylaxis
• Thrombosis
• Renal failure
• Hypotension
• Nausea
• Vomiting
• Diarrhea
• Fever

Interactions

• Potential interaction with anticoagulants which may increase the risk of bleeding
• Caution is advised when used with other medications that affect coagulation

Precautions

• Monitor renal function during treatment, especially in patients with pre-existing renal impairment
• Use with caution in patients with a history of bleeding disorders
• Careful assessment of the benefits versus risks in patients with cardiovascular conditions

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Aprotinin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether aprotinin is excreted in human milk. Caution should be exercised when administering aprotinin to a nursing mother.

Storage

Store in a refrigerator (2-8°C). Protect from light. Do not freeze.

Formulations

• Injection: 10,000 IU/mL
• Injection: 50,000 IU/mL

Mechanism of action

Aprotinin inhibits serine proteases including trypsin, chymotrypsin and plasmin at a concentration of about 125,000 IU/mL, and kallikrein at 300,000 IU/mL. The inhibition of kallikrein inhibits formation of factor XIIa. This inhibits the intrinsic pathway of coagulation and fibrinolysis. Inhibition of plasmin also slows fibrinolysis. Aprotinin 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. Aprotinin, through its inhibition of multiple mediators (e.g., kallikrein, plasmin) results in the attenuation of inflammatory responses, fibrinolysis, and thrombin generation. Aprotinin inhibits pro-inflammatory cytokine release and maintains glycoprotein homeostasis. In platelets, aprotinin 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 aprotinin use in ... /cardiopulmonary bypass/ 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. Aprotinin is thought to improve hemostasis during and after cardiopulmonary bypass by preserving platelet membrane receptors that maintain the adhesive and aggregative capacity of platelets. In addition, aprotinin inhibits fibrinolysis through inhibition of plasmin and plasma and tissue kallikreins. Because of its effects on kallikrein, aprotinin also inhibits activation of the intrinsic clotting system (i.e., contact phase of coagulation), a process that both initiates coagulation and promotes fibrinolysis. The relative contribution of these effects of aprotinin to the drug's therapeutic action remains to be fully elucidated. For more Mechanism of Action (Complete) data for APROTININ (6 total), please visit the HSDB record page.

Pharmacodynamics

Aprotinin 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. Aprotinin, through its inhibition of multiple mediators [e.g., kallikrein, plasmin] results in the attenuation of inflammatory responses, fibrinolysis, and thrombin generation. Aprotinin inhibits pro-inflammatory cytokine release and maintains glycoprotein homeostasis. In platelets, aprotinin 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 aprotinin 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.