1. Aprotinin
Emily Sarver
11/20/2018

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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