Why can't you give tPA after 3 hours?

[cardsurgguy]

Hey, quick question for the neuro folks out there...

I was working at my job last week when a guy came in with a stroke into the ER
We initiated protocol and sent him for CT, got bloods appropriate for tPA like PT/PTT and INR

At first, the neuro resident wasn't going to give tPA since he was on coumadin, but his INR came back kind of low (1.4), so it was decided to give him tPA

So anyways, we were going to give him tPA since the time was about 2 hrs 40 minutes, but then the family member said she wasn't sure if the symptoms start at the original time she told us, and she said they might have started 30 min earlier which would have been 3 hrs 10 minutes

This is out of the tPA window of 3 hrs, so we didn't give it to him


My question is, what happens, physiologically speaking, with the stroke that makes it so you can't give tPA after 3 hrs after the start of symptoms when it's fine before 3 hrs?

I'm not particularly interested in neuro as a career (as my name would suggest), but I find every field of medicine interesting, and have been curious about this question since last week...

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[Pinky]

From the instant one has the stroke to the three hour mark, the possible benefit of giving TPA outweighs the possibility of having an intracranial bleed. As each minute passes, the benefit decreases and the risk increases. After three hours, the risk of intracranial bleeding outweighs the benefit of giving TPA.

 

[Lesion Of Doom]

From the instant one has the stroke to the three hour mark, the possible benefit of giving TPA outweighs the possibility of having an intracranial bleed. As each minute passes, the benefit decreases and the risk increases. After three hours, the risk of intracranial bleeding outweighs the benefit of giving TPA.

In other words, if you like to avoid huge lawsuits, try to keep the tPA within the 3 hours.

I often hear stories about how the patient received tPA just as the clock was ticking down to the 3 hour mark. I wonder if someone screws with that clock sometimes to keep it at 2:59.

 

[refmem]

Nothing says you can't give IV-tPA after 3 hours, however the NINDS study choose 3 hours as the cut-off time in their protocol basically because someone thought after 3 hours there would be no viable brain tissue left in the infarcted territory. Spurring this decision were the European thrombolytic trials which did not show much benefit to IV-thrombolytics given within a much broader timespan from symptom onset.

If you look at the NINDS trial, you will see that most patients that benefitted from IV-tPa were amdinistered the drug within 90minutes of symptom onset, however the study was not designed in a way that allowed this subgroup statistic to stand out. Nonetheless, the benefit of IV-tPA given within 3 hours of symptom onset was shown and this is what earned FDA approval.

Intra-arterial tPA can be used up to 6 hours after symptom onset for anterior circulation infarcts and sometimes up to 12 hours after onset in posterior circulation strokes. While the infarcted tissue may not be viable, it has been suggested that intra-arterial tPA within these timeframes may help preserve prenumbral tissue at risk for infarction. Again, these timelines are nice, round, numbers pulled out of thin air.

For your case, I would have a hard time using IV-tPA on anyone on coumadin regardless of their INR, as you may not know when they took the last dose and if they took that dose correctly. NINDS excluded patients on oral anticoagulation from the study group, so there is no proven benefit. Your patient may have been a candidate for intra-arterial tPA if offered at your site.

 

[refmem]

From the instant one has the stroke to the three hour mark, the possible benefit of giving TPA outweighs the possibility of having an intracranial bleed. As each minute passes, the benefit decreases and the risk increases. After three hours, the risk of intracranial bleeding outweighs the benefit of giving TPA.

While the NINDS study did suggest more benefit of IV-tPa when used sooner after symptom onset, no data suggested that the risk of ICH is increased at 3 hours compared to, say, 1 hour. Chances are, the risk of ICH is probably the same regardless of when you give IV-tPa. When you state "As each minute passes, the benefit decreases and the risk increases", I assume you mean relative risk, not the absolute risk.

Also keep in mind that there was no significant difference in mortality in the patients who received placebo versus the patients who received IV-tPA (and may have had a ICH). Remember that both treated and nontreated groups are at risk for ICH.

 

[Methyldopa]

Nothing says you can't give IV-tPA after 3 hours, however the NINDS study choose 3 hours as the cut-off time in their protocol basically because someone thought after 3 hours there would be no viable brain tissue left in the infarcted territory.

My understanding is that in NINDS, they found that the average time in which tPA was given during the investigation was around 3 hours. Hence the 3hrs.

This is similar to the 8 hour window for steroids given post-traumatic spinal cord injury (which indeed is arguably a useless treatment). In that study they found that the closest time the investigators gave steroids was around 8hrs.

 

[EM Junkie]

While on the stroke service at Memorial-Hermann Hospital in Houston (a regional stroke center), tPA was frequently given outside of the window as "compassionate tPA". Basically, family members consented that death was better than living like that, etc, etc.

Never saw it work though!!