Aprotinin Emily Sarver 11/20/2018

Background 600,000 people in US undergo heart surgery per year 30% require blood transfusion Blood transfusion is a strong predictor of mortality 77% increased risk of death Conservation of blood is important… Shortage of donor blood Risk (infection, death) Cost 11/20/2018

Background CPB circulates and oxygenates the blood CPB increases the risk of transfusion Coagulopathy Hemodilution Entire blood mass is anticoagulated + exposed to extracorporeal materials This interface results in… Activated coagulation proteins Decreased platelet count and function Activation of systemic inflammatory response Basically – hemostasis is transformed into chaos 11/20/2018

Aprotinin (Trasylol) Antifibrinolytic used to decrease bleeding FDA approved since 1993 Slows down fibrinolysis Decreases need for blood transfusions during surgery Decreases end-organ damage due to blood loss 11/20/2018

Mechanism of Action Strongly inhibits plasmin (inhibits fibrinolysis) Blocks conversion of kininogen to bradykinin (inflammatory mediator) Inhibits activation of C1 of the complement system Preserves the adhesive glycoproteins in platelets Increases resistance to damage Allows platelet adhesion to endothelium Prevents expression of pro-inflammatory glycoproteins in granulocytes 11/20/2018

Benefits of Aprotinin Blood loss reduction of 40-50% Reduction in blood use 40-80% May decrease systemic inflammatory reaction to CPB 11/20/2018

Adverse Effects Study in NEJM in 2006 with 4,374 patients 1:200 risk of anaphylaxis Doubled risk of renal failure Forces 10,000 patients of dialysis each year 55% increased risk of MI or heart failure 181% increased risk of stroke or encephalopathy 11/20/2018

Adverse Effects Untoward events for 1st exposure 1:143 Untoward events for 2nd exposure 1:11 Side effects have incurred more than $1 billion in medical costs per year! 11/20/2018

Alert! Feb. 2006, FDA issued public health advisory Possible renal and CV toxicity Currently, use of Aprotinin is at physician’s discretion 11/20/2018

Conclusion Do the benefits outweigh the risks????? What about the risk of receiving blood + aprotinin? Should Aprotinin’s use be at the physician’s discretion? What about safer alternatives? Do the benefits outweigh the risks????? 11/20/2018