CABG/Bypass

[sevoflurane]

I'm far away from my cardiac rotation, but I had a question I was hoping someone could explain for me.

So... Aprotonin is an antifibrinolytic and heparin is an anticoagulant. Why run both of these at the same time? It seems counter-intuitive to me. I know they are seperate systems but one inhibits clot lysis and the other makes them prone to bleed. Right? I know I'm missing something here.

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[Idiopathic]

I'm far away from my cardiac rotation, but I had a question I was hoping someone could explain for me.

So... Aprotonin is an antifybrinolytic and heparin is an anticoagulant. Why run both of these at the same time? It seems counter-intuitive to me. I know they are seperate systems but one inhibits clot lysis and the other makes them prone to bleed. Right? I know I'm missing something here.

I was told that the trasylol helps with the various problems with the pump...the oddities in coagulation that occur with bypass. The coag system is so incredibly complex that an anticoag at one place can actually promote clotting down the line if everything isnt in balance. The rep just tried to say that clotting factors get 'chewed up' during the procedure and trasylol helps keep the system more stable, allowing the heparin, etc. to work more effectively. I think the lines in the pump can also leech out some of the clotting factors and this is supposed to help prevent that too.

Anyway, apparently is falling out of favor in PP entirely. I expect it to remain in academics for a while longer but all the bigwigs around here are already over it.

 

[Gator05]

I understood Amicar/Aprotinin to be serine protease inhibitors. Without going back and reading up on it, can minimize pump-induced inflammation, as well as block plasmins and other protein clot-busters. Thus, with heparin, you prevent extension of new clots, and amircar/aprotinin prevent lysis of existing ones. Probably a super-gross simplification, but there you have...something.

By the by, please let me know if you ever get a perfect explanation of how the clotting cascade "really" works. Usually after 20 minutes it gets so bogged down in details...We have some new educational models/tools coming online here at UF, you can check them out at the sim site.

 

[Laryngospasm]

I'm far away from my cardiac rotation, but I had a question I was hoping someone could explain for me.

So... Aprotonin is an antifibrinolytic and heparin is an anticoagulant. Why run both of these at the same time? It seems counter-intuitive to me. I know they are seperate systems but one inhibits clot lysis and the other makes them prone to bleed. Right? I know I'm missing something here.

I believe the desired end result is reduced post op bleeding and transfusion requirements.

 

[sevoflurane]

I believe the desired end result is reduced post op bleeding and transfusion requirements.

Isn't aprotonin hung towards the begining of the case? I would think it would make sense to hang it at the end of the case to prevent post op bleeding as you say. Hmmm....

 

[Laryngospasm]

Isn't aprotonin hung towards the begining of the case? I would think it would make sense to hang it at the end of the case to prevent post op bleeding as you say. Hmmm....

Thought to preserve platelet function, and thus decrease transfusion requirements, decreased incidence of perioperative stroke also I think.

 

[nimbus]

http://content.nejm.org/cgi/content/short/354/4/353

Sorry I don't have link to full text, but this is why aprotonin is coming out of favor. Retrospective study but compelling nonetheless. Increased renal failure, MI, CHF, CVA and increased death. Also, it is over $1000/dose vs a few dollars for amicar.

 

[Idiopathic]

.We have some new educational models/tools coming online here at UF, you can check them out at the sim site.

The most fun I had during interviews was at your sim lab.

 

[BIS]

Aprotinin directly inhibits plasmin which screws up GpIIb/IIIa plat receptors and causes fibrinolyis which you dont want post CAB. it also inhibits thrombin which causes activation and irreversible secretion of granule contents such as TXA ect. Preventing this activation preserves its fxn.

It also inactivates factors VIIa, VIIIa. The herparin is needed to enhance Antithrombin which inactivates IX, X, XI, XII, II. The aprot protects the plats and is an antifibrinolytic yet its anticoag effect is not extensive so heparin is needed. Heparin is synergized by aprot.

Aprot also inhibits kallikrein which can also convert plasminogen to plasmin.

Plasmin also serves to activate complement C3 to C3a which increased vascular permiability.

The aprotinin article claiming increase thrombosis is a little fishy. It seems as though someone representing amicar was paid to rip on, aprotinin. They claim that since aprot inactivates protein C which normally inactivates factors VIII, V, and plasminogen activator inhibitors that it can lead to thrombosis. When reading the article however I have my doubts. The data seems skewed.

 

[sevoflurane]

Aprotinin directly inhibits plasmin which screws up GpIIb/IIIa plat receptors and causes fibrinolyis which you dont want post CAB. it also inhibits thrombin which causes activation and irreversible secretion of granule contents such as TXA ect. Preventing this activation preserves its fxn.

It also inactivates factors VIIa, VIIIa. The herparin is needed to enhance Antithrombin which inactivates IX, X, XI, XII, II. The aprot protects the plats and is an antifibrinolytic yet its anticoag effect is not extensive so heparin is needed. Heparin is synergized by aprot.

Aprot also inhibits kallikrein which can also convert plasminogen to plasmin.

Plasmin also serves to activate complement C3 to C3a which increased vascular permiability.

The aprotinin article claiming increase thrombosis is a little fishy. It seems as though someone representing amicar was paid to rip on, aprotinin. They claim that since aprot inactivates protein C which normally inactivates factors VIII, V, and plasminogen activator inhibitors that it can lead to thrombosis. When reading the article however I have my doubts. The data seems skewed.

Nice job BIS

 

[SilverStreak]

I believe the desired end result is reduced post op bleeding and transfusion requirements.

Many people don't realize also a long pump run on the bypass machine can contribute to postop bleeding. Running the patient's blood through the pump causes inflammation and lysis as others have mentioned, but also the crystalloids used to flush the system can wash out some of the coag factors. Also, if they have trouble coming off pump and have to go back on and off, the exact amount of heparin may not be kept up with, so when you go to reverse it, you may only be giving enough protamine for half of the amount of heparin that was really given when they went back on pump the 2nd or 3rd time.

Most of our surgeons are still using the trasylol. If it is the same article you are referring to that was published in the New England journal, a few of them have stopped using it until further results come out to verify what that study found.

 

[sevoflurane]

Spoke briefly with one of our Cardiac anesthesia attendings today, and as mentioned above, it does indeed decrease inflamation and post-operative cognitive dysfunction tends to be reduced. He was impressed by it when he first used it due to the ability of keeping a dry field, a benefit that, according to him, is not very much appreciated. It does decrease post-op bleeding and he thinks that the New England article is suboptimal. We still use it routinely at our institution.

 

[nimbus]

Aprotinin directly inhibits plasmin which screws up GpIIb/IIIa plat receptors and causes fibrinolyis which you dont want post CAB. it also inhibits thrombin which causes activation and irreversible secretion of granule contents such as TXA ect. Preventing this activation preserves its fxn.

It also inactivates factors VIIa, VIIIa. The herparin is needed to enhance Antithrombin which inactivates IX, X, XI, XII, II. The aprot protects the plats and is an antifibrinolytic yet its anticoag effect is not extensive so heparin is needed. Heparin is synergized by aprot.

Aprot also inhibits kallikrein which can also convert plasminogen to plasmin.

Plasmin also serves to activate complement C3 to C3a which increased vascular permiability.

The aprotinin article claiming increase thrombosis is a little fishy. It seems as though someone representing amicar was paid to rip on, aprotinin. They claim that since aprot inactivates protein C which normally inactivates factors VIII, V, and plasminogen activator inhibitors that it can lead to thrombosis. When reading the article however I have my doubts. The data seems skewed.

It's really unlikely anyone "represents" amicar or tranxemic acid. Both agents are decades old, generic and cheap. It's not like Desflurane vs. Sevo. (Remember the sevo-->renal failure BS sponsored by Baxter?) I know there are some prospective trials of antifibrinolytics in the pipeline. Hopefully they will clarify the picture for all of us.

 

[rn29306]

I understood Amicar/Aprotinin to be serine protease inhibitors.

Amicar is not a serine protease inhibitor. Amicar acts as a fibrinolysis inhibitor with a MOA understood to be inhibition of plasminogen activators (ie. plasminogen to plasmin).