tPA in setting of elevated INR

[NeuroDocDO]

Would you reverse a patient with an INR of >1.7 who is on coumadin for afib that comes in with an NIHSS of 7 and is within the 3 hour window with otherwise no other contraindications for IV tpa? Do you give this patient FFP to try to get their INR in a more favorable range so that you can administer IV tPA or do you just exclude them from IV tPA since the INR is elevated?

Thanks,

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[typhoonegator]

No. Do not reverse. Do not treat. Reversing INR does not necessarily reverse coagulopathy, and there is no precedent for doing this. You would be way off-label. There is a reason why we don't give people tPA in the 4.5 hour time window if they are on coumadin -- regardless of the INR. Also, unless they had their stroke 5 minutes ago, by the time you thaw FFP, transfuse it (a lot of volume) and then recheck the INR, you're going to be up against the window anyway. I might take them to IA though, if they had a cutoff.

Neurology. 2012 Jul 3;79(1):31-8. Subtherapeutic warfarin therapy entails an increased bleeding risk after stroke thrombolysis (PMID: 22649217)

 

[Hank Rearden]

Agree with not giving FFP, but many more aggressive neurologists would give the TPA. Personally I would be on the fence on this one, but would probably advocate giving it. Keep in mind the higher the NIHSS, the higher the bleeding risk, and if there were any early changes on head CT I would absolutely not give it. At AAN this year I went to the Stephen Mayer led stroke alert workshop, and many in that group were advocating TPA for clear cut case if INR < 2. Yes, this is off label. I know that someone is trying to start a multicenter trial looking at answering this question specifically. Many think that giving IV-TPA even in the setting of therapeutic coumadin levels may be beneficial.

 

[neglect]

This is an excellent question and it should be an active area of research. And if there were a trial, I'd be fine with enrolling a subject.

That said, I would be extremely uncomfortable given tPA to an anticoagulated patient from any source. I have given a single patient tPA after 48 hours off LMWH after I spoke to heme.

I think if you do this, then you are in severe danger of litigation or increasing M&M. Note that general rule: anti-coagulation does not make people bleed, it prevents them from clotting - that's a difference. Knowing that they don't clot, giving them a drug that CAN make them bleed increases iatrogenic damage. So I'd never do it clinically.

 

[danielmd06]

Would definitely not give IVtPA, nor would I try to reverse an elevated INR for the purpose of giving IVtPA.

Our protocols in residency were not to administer the drug for an INR of 1.5 or above. In an appropriate patient you could consider endovascular interventions, however.

 

[Hank Rearden]

I misread, thought OP said INR = 1.7. I stand by my claim that 1.7 < INR < 2 is a gray area for some more aggressive neurologists.

 

[burs0028]

I think Neurologists or other stroke practitioners who ask questions about reversing INR to allow for tPA infusion are missing the point.

Your patient has a known propensity towards formation of clots; this is why they were prescribed anticoagulation and was likely a significant actor in forming the current clot in their brain.

Reversal efforts will further imbalance their hematologic system toward a clot-forming tendency and possibly hinder or eliminate any chance of your patient's natural fibrinolytic system from working appropriately and lysing the clot--it might even make the infarct worse by encouraging the thrombus to propogate when it would be less likely to do so at the higher INR. It's understandable you want to give tPA and increase the chance of that clot dissolving, but why would you further imbalance your patient's coagulation system toward clotting prior to doing so?

Obviously the full cascade of events that determine whether your blood clots or not is incredibly complex and I, nor any other non-hematologists on this board cannot reasonably claim to fully understand the system, but based on my relative level of knowledge and expertise I simply cannot understand the reasoning behind such actions.

As other posters have indicated, if it's a large vessel occlusion you could try IA thrombectomy, but at an NIHSS of 7 this is debatable; otherwise you have to cross your fingers like our predecesors did and wait to see what happens.

Am I missing something here guys???

 

[bustbones26]

I'd give them viper venom!!! Oh wait, they canned that project, nevermind!!

Whenever it comes to tPA, my experience is that you have many split on this. Some will do everything possible to reason out why a patient is NOT a candidate because they are so uncomfortable giving tPA, while others would tPA a goat if it was brought into the ER with hemiparesis.

I tend to think in terms of legal medicine. INR>1.5 is exclusion, period!!! Yeah, I know its disappointing that in this case the patient was on the border, but what can you do? As typhoonegator had said, by the time you give them FFP, you are eating up clock time.

If my hospital had a strong neurovascular program with cath jockies running around, I certainly would give them a call and ask their opinion on the IA window or work the patient up in the ER for large occlusion to determine if they are a clot retrieval candidate, but for IV tPA, I just would not do it!!

But how about this for a twist? If they were on coumadin and suptherapeutic, (INR<1.5) would you do it?

 

[typhoonegator]

But how about this for a twist? If they were on coumadin and suptherapeutic, (INR<1.5) would you do it?

Absolutely, but only in the 3 hour window. The largest study on the topic did not show an increased hemorrhage rate for those on warfarin with INR < 1.7:

Stroke. 2011 Apr;42(4):1041-5.

A very recent study does suggest an increased hemorrhage rate, but in a smaller group of warfarin subjects:

Neurology. 2012 Jul 3;79(1):31-8.

I would certainly counsel the patient/caregiver, but the medication is FDA approved for that indication, and there is scientific backing for the decision. At 1.5 I would treat.

 

[danielmd06]

But how about this for a twist? If they were on coumadin and suptherapeutic, (INR<1.5) would you do it?

Definitely (but specifically within 3.0 hrs like TN said - not the 4.5 window). The INR is less than 1.5 so I'd give.

 

[danielmd06]

Absolutely, but only in the 3 hour window. The largest study on the topic did not show an increased hemorrhage rate for those on warfarin with INR < 1.7:

Stroke. 2011 Apr;42(4):1041-5.

A very recent study does suggest an increased hemorrhage rate, but in a smaller group of warfarin subjects:

Neurology. 2012 Jul 3;79(1):31-8.

I would certainly counsel the patient/caregiver, but the medication is FDA approved for that indication, and there is scientific backing for the decision. At 1.5 I would treat.

So you would not treat at 1.7 or above, and would treat at 1.6 or below (within 3.0 hrs) based on the study? Just curious what you guys are doing up in New England.

 

[typhoonegator]

So you would not treat at 1.7 or above, and would treat at 1.6 or below (within 3.0 hrs) based on the study? Just curious what you guys are doing up in New England.

We treat in the 3 hour window based on standard IV tPA criteria, which include INR less than or equal to 1.7, regardless of warfarin status. There is some inter-individual variation in this practice, but for the most part we try to err on the side of treating. In the 4.5 hour window, anyone on warfarin, regardless of their INR, is not a candidate for thrombolysis. There is data to support this position, as I have noted above, as well as the original tPA trial criteria which also supported this cutoff.

That said, I don't like these sort of cases because there clearly is a continuum of risk and an INR of 1.7 is going to be less safe than 1.0, but you have to draw a line somewhere. It's not like there is a physiologic reason why 1.6 is just fine and 1.8 is not. I factor something like a warfarin-elevated INR into my overall decision, and if there is a suggestion of clot migration (early ischemic reperfusion) or anything else that would steer me relatively against tPA, then I make a decision on those relative merits.

As I mentioned above, INR is not an absolute measure of coagulation ability. It is a very rough metric. Warfarin patients, even those with INR < 2 or 1.7 or whatever, are relatively coagulopathic. I always discuss this with the patient or surrogate when counseling them about whether or not I recommend tPA.

By the way, this is a GREAT discussion, and it's a lot of fun to hear all of the perspectives. Mine is just one of many, even if it is coming out of "New England".

 

[Hank Rearden]

Not trying to hijack the thread, but this one seems to have run it's course. Here's another situation that comes up occasionally and seems to be a gray area. I'm curious to know what others do around the country. Acute stroke patient comes in, hx of A-Fib, on coumadin. Let's say they have a moderately sized hemispheric stroke with NIHSS 10-15. The INR comes back at 2 and they're 14 hrs from sx onset, so not a good candidate for IV-TPA or IR. Do you reverse their coagulopathy to prevent hemorrhagic conversion, and if so, with vit K or FFP? If you do reverse them, when do you restart coumadin?

Personally, I would give vitamin K in this instance and restart coumadin in 1-2 weeks. If it was a smaller stroke, I would not give vitamin K and just keep them therapeutic on the coumadin.

 

[danielmd06]

Not trying to hijack the thread, but this one seems to have run it's course. Here's another situation that comes up occasionally and seems to be a gray area. I'm curious to know what others do around the country. Acute stroke patient comes in, hx of A-Fib, on coumadin. Let's say they have a moderately sized hemispheric stroke with NIHSS 10-15. The INR comes back at 2 and they're 14 hrs from sx onset, so not a good candidate for IV-TPA or IR. Do you reverse their coagulopathy to prevent hemorrhagic conversion, and if so, with vit K or FFP? If you do reverse them, when do you restart coumadin?

Personally, I would give vitamin K in this instance and restart coumadin in 1-2 weeks. If it was a smaller stroke, I would not give vitamin K and just keep them therapeutic on the coumadin.

Excellent question! This area of clinical care is amongst my favorite topics, and there really seems to be a dearth of information provided anywhere (haven't read that Stroke Continuum yet). Actually, what you outlined is close to what I would have done as a resident under my stroke attendings. The major focus was the size of the stroke in these cases for us. Large strokes (or ICH from hypertension or amyloid) would have the coumadin held/reversed and not restarted for a good 2-3 weeks. Then restarted slowly without heparin gtt. The paradoxical hypercoagulability at anticoagulation restart was explained to the patient, too.

From an academic standpoint, I would be very interested to hear what others think about these situations. What are your stroke size cutoffs? What were the INR determinants your department used? Etc. There is sparse literature to my knowledge on this topic.

While we've hijacked the thread and I'm casting pride to the wind, I would also ask if anyone has article/literature suggestions or links to share, too. I just cannot seem to ever get tired of reading about this topic.

 

[typhoonegator]

Do they have ischemic reperfusion or not?

 

[Mattchiavelli]

I would also add taking into consideration the patient's diabetes status and their history of good control or not, if I'm not mistaken sugary arteries are more prone to hemmhorage.

 

[Hank Rearden]

In response to Typhoonegator - that knowledge wouldn't change my management. Would it change yours? How so?

 

[danielmd06]

If anyone is interested the INR cutoff values were discussed a bit in the latest issue of Neurology Today.

 

[typhoonegator]

In response to Typhoonegator - that knowledge wouldn't change my management. Would it change yours? How so?

Weeeell, I'm not big on reversing overall. They already had a stroke through anticoagulation, why would you want to make them even more pro-coaguable without a very good reason? Being scared isn't a good enough reason.

Ischemic reperfusion into a hemispheric stroke or large PICA stroke always gives me pause, however. Those people do seem to bleed more, although I don't have Big Data to back that up, other than some of the re-flow data from IV and IA thrombolysis. Even an HI1 would be enough to make me reverse, and a lot of these folks will have some petichial bleeding, so once you see that on the CT you're going to reverse anyway.

But the big reason I typically reverse those patients is because the ischemic reperfusion increases edema in the dead tissue, which increases mass effect, and increases the chances that I'm going to ask for a hemicrani (or SOC for a PICA-AICA). For those folks, I reverse early to make sure they are tee'd up for the OR. The caveat is that some of these patients I'd reverse even without evidence of early recanalization if they look terrible and I think they'll need to go get their bone off.

Bottom line, a small superior division MCA stroke with no conversion and early reperfusion, nah, wouldn't reverse acutely. Big stroke with OR concerns, yeah, ischemic reperfusion/early recanalization would probably make me more likely to reverse, but purely for practical reasons as stated above.