The drama of using tPA in stroke within the three-hour window

Before telling this story, I’m going to have to lay some background for my non-medical readers.

The most obscene word in English, in my opinion, has three letters and is an acronym. It’s tPA (it stands for Tissue Plasminogen Activator).

This drug gets a lot of press as a “clotbuster.” It has the potential to break down clots and reverse a stroke. That potential, however, has a dark side. By breaking down clots it can also cause catastrophic bleeding into the brain.

As a result, I’m not a fan of this drug. I use it very judiciously, with a solid understanding by the family and patient of what they are getting into. It can lead to both great rewards and serious complications.

Compounding this is the fact that the drug must be given within three hours of a defined stroke onset, or the risk of bleeding really goes up. So if I’m told that the symptoms started at 1:45, then a clock immediately starts running, and if the drug isn’t given by 4:45, then it’s not going to be given. In that three hour window I need to get to ER, confer with the emergency physician, assess the patient, get a CT scan and labs, explain the situation and drug (and it’s dangers) to the patient and family, and get their understanding, and approval (or refusal) to give it.

Those three hours become a very frantic, fast-paced blur. It’s even worse if the patient gets to ER one hour after an event, meaning I only have two hours to work with.

And with that background, I now present tPA – A Play, which was performed this weekend at local hospital.

Our play opens in ER, where our hero, Dr. Grumpy, has just arrived. The patient is an elderly gentleman with abrupt onset of speech difficulties and right-sided weakness at noon. He got to ER at 1:30, our hero was called at 1:45, and arrived in ER at 2:00. He hurriedly examined the patient and met with the wife, and then discussed the risks and benefits of tPA.

(Curtain rises)

2:15 p.m. Dr. Grumpy: “What are your thoughts about this treatment, or any other questions?”

Mrs. Smith: “Let me call our children.”

Mrs. Smith then whips out a cell phone, frantically calling people all over the country, leaving messages on their voice mail, then calling back to see if they’ve picked up their voice mail yet. Dr. Grumpy wanders back to nurses’ station to review labs.

2:22 p.m. Nurse says wife wants Dr. Grumpy to come discuss this with the patient again. Because of the stroke Mr. Smith is unable to speak or understand speech, but Dr. Grumpy attempts to do so anyway. He reminds Mrs. Smith of the urgency of the situation. She continues to make phone calls. Dr. Grumpy goes back to nurses station.

2:28 p.m. Mrs. Smith reaches a daughter, and tries to explain situation to her. Then gives cell phone to Dr. Grumpy to explain to daughter.

2:29 p.m. Daughter becomes hysterical and asks to talk to her mother again.

2:31 p.m. Mrs. Smith hands phone to Mr. Smith, and tells him to explain his symptoms to the daughter. The unfortunate stroke patient can’t speak, just stares at phone, saying nothing. Dr. Grumpy leaves the room to keep from breaking down, again reminds wife of urgency.

2:35 p.m. A four-minute attempt to get Mr. Smith to talk to daughter on cell phone ends, with no decision. Highlight was when Mrs. Smith turned up the volume on the cell phone, figuring that might help patient understand daughter better. The look on Mr. Smith’s face makes it apparent he’s suddenly regretting his choice of spouse.

2:38 p.m. ER volunteer says wife wants Dr. Grumpy to come back and explain to patient for second time what is going on. He good-naturedly attempts to do so. Mrs. Smith repeats everything Dr. Grumpy says, screaming loudly into patients ear, hoping that will help. Again reminds wife of urgency.

2:41 p.m. Parents of screaming child in room next door ask Mrs. Smith to stop yelling at Mr. Smith, as it’s upsetting their child. She goes into their room to argue with them.

2:43 p.m. Mrs. Smith starts making more phone calls. Dr. Grumpy reminds her of urgency.

2:46 p.m. Mrs. Smith somehow decides that the reason she can only reach voice mails is because the cell phone reception inside the hospital is poor.

2:47 p.m. Dr. Grumpy goes back to see if Mrs. Smith has made a decision. Discovers she’s absent from room.

2:49 p.m. Dr. Grumpy and nurses stand at window, incredulously watching Mrs. Smith walk across the street and get in line at a Starbucks, still frantically dialing phone numbers.

2:55 p.m. Mrs. Smith gets a coffee and starts coming back to ER. She walks in front of an oncoming ambulance, which slams on it’s brakes and swerves to avoid flattening her. Mrs. Smith goes over and pounds on the driver’s side window to cuss out the driver, arguing with him in the middle of the street.

2:58 p.m. Mrs. Smith attempts to enter ER again through ambulance entrance, which only opens for a paramedic or hospital ID. She frantically knocks and waves at the paramedic who she just finished cussing out. They get into another argument about which of them needs to pay better attention.

3:01 p.m. Mrs. Smith finally finds way back to patient room, asks nurses to call Dr. Grumpy.

3:03 p.m. Mrs. Smith says she’s made a decision. She wants to do whatever Dr. Grumpy thinks she should do. Dr. Grumpy informs her that he is not going to do anything, as the tPA window has closed.

(Curtain falls)

Doctor Grumpy is a neurologist who blogs at Doctor Grumpy in the House.

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  • Major Moore

    Considering that the brain hemorrhage rate for intravenous tPA is 6 percent, the patient’s family was foolish in gambling with the patient’s outcome. Doesn’t the doctor have any obligation to give these statistics to the family if indeed the hemorrhage factor was a stumbling block in deciding the course of action for the patient?

  • AG

    Decision by default. I hope that you would give the patient’s wife/surrogate decision maker a deadline, and made it clear that after that deadline you would be making the decision based on what you thought was best for your patient. Clearly with the prep that had to be done prior to administering tPA you either needed a decision well before 3:00, or to begin the preparation process without having made the final call yet. It sounds like in the end you got what you wanted for the patient (no tPA) anyway. In this scenario, did you ever give your recommendation? I’ve noticed a trend lately when I go to the doctor that they lay out options and just sit there, without having given a recommedation. While I don’t expect to be “ordered” to allow a specific option, I do expect to get a recommendation.

  • This is just unreal. Please assuage my faith in the average human being and say that this didn’t happen.

  • cynical

    I have never seen so much hype and promotion about a drug that has marginal benefit at best. A reanalysis of the original NINDS data is presented in this months Annals of EM. It is just so underwhelming. Yet doctors continue to get sued for giving and not giving. All it is is a wet dream for trial lawyers.

    tpa for stroke, unproven CMS core measures–those are the two things that have me seriously wanting to quit being an ER doc.

  • Happy Hospitalist

    I guess the decision was made for you. What are you complaining about?

  • Dr. Grumpy

    Unfortunately, the story is true. The wife was obviously someone who was incapable of making decisions without extensive consultations with family, and in this case she had no support system. So basically, as AG put it, it became “decision by default”.

    TPA is not a decision that I, or any other neurologist I know, would make for the family, regardless of how inane their behavior was. A bad outcome made without their consent will get you sued, and in some states could constitute medical assault/battery.

  • cynical

    This happens all the time. Why is that so unbelievable? It doesn’t matter anyway because the evidence fo tpa is paultry. It is not the magic bullet or fairy dust that people think it is. All it has done is raise costs, enrich lawyers, and place ER docs in a catch 22 legal hell. This family was lucky that there was even a neurologist in to help with the case. In most community hospitals you won’t get that. Even though a lot of neurolgists sing the praises of tpa most neurologists out in Anytown, USA don’t want to touch this with a ten foot pole.

  • PharmNerd

    Haven’t you heard? You can give tPA up to 4.5 hours now…
    Not terribly efficacious after 3hrs, though…

    Our hospital has actually gone gung-ho with intra-arterial tPA & clot extraction devices lately, which extends the window to 6-8hrs+. Outcomes are typically really good, or really bad.

  • cynical

    Lets see. All previous analysis was that given outside of 3 hrs was a protocol violation and had bad outcomes. One poorly interpreted study wants now says the protocol violation is good? That is like saying that if the Clippers beat the Lakers once they are a better team. Negetive studies don’t get the practice changing attention they should. NINDS was just one barely positive study out of many negetive trials with thrombolytics.

    UCLA is publishing the data on use of intra-arterial tpa and extraction devices and it just is not rosy.

  • Dr. Grumpy

    Agree with you, Cynical.

    While there are many reasons, TPA is one of the big ones driving me to phase out my ER coverage.

  • Joe

    From Cynical: “I have never seen so much hype and promotion about a drug that has marginal benefit at best.’

    You are on target there

    Most new stuff is nothing but hype about marginal benefits. Me-too drugs, drugs for non-diseases like “Overactive Bladder Syndrome”, … . But try telling a patient that the treatment they saw advertised and then read about on the company’s website isn’t all its cracked up to be.

    The real health-care reform would be to stop direct to consumer advertising for anything related to health care.

  • SarahW

    My understanding is that the Tpa window has been established to be much wider than 3 hours, and that significant benefits can be obtained for several hours past this earlier window.

    Why would you delay determining if someone is having a bleeding vs. clot stroke within this window, since it is what holds back decisions in the first place?

  • SarahW

    Here is a link to reporting on the “wider window” for use of TpA link that I referred to.

  • Bob

    Having a sibling who waited 24 hours while having a stroke in a multi-group hospital ER which had treated her for prior strokes and had a “certified stroke center” within 10 miles of the location of the attending hospital ER, your story is less than compelling.

    I don’t know where the “3 hour window” comes from as in former times it was 6 hours and a simple proceedure to provide the ER would be standing orders for that staff to do a CT as soon as the stroke symptoms are encountered, for this must be done to see if tPA use is warrented and safe.

    My understanding is that “mini strokes” are a precurser to strokes and that family history is a strong indicator and futher that some 80% of total strokes would benefit from use of tPA. Knowing this I demanded that the product be used and was denied it’s use because the doctor on ER staff refused [the neurologist wasn't available and the nearby stroke center which has one 24/7 wasn't contacted, couldn't travel 10 miles or couldn't leave the other "certified" hospital without a fully staffed stroke unit" ] .

    So after weeks of PT, my sister was transferred to a nursing home where she is “watered” 3 times a day through a feeding tube and placed in a wheelchair with scores of other stroke patients, Because physicians don’t want to make a mistake and continue a system that choses a domoralizing life over a 80/20% beneficial treatment!

    I urged the family to sue for malpractice since her arrival time at the hospital was 15 minutes and malpractice is limited to a $1million amount in this state as she literally suffered her stroke almost entirely in that ER. Physicians and institutions should not gain malpractice reform and if they want it should be required to handle their own reform by correcting their own smallnumber of problem doctors and most institutions. To not do so just masks the problems and allows malpractice tio continue to be more the norm.

  • David

    Dr. Grumpy,

    I’m supportive of using IV-TPA even though the benefits are small. Why not do what is in the patient’s best interest, even if marginally so?

    As has been pointed out, there is now a recommendation to use a 4.5 hour window, albeit with more restrictions, including an age restriction (80 years).

    Of course intra-arterial TPA has a 6 hours window; and then there is Penumbra and Merci devices too – which may not have been available in your hospital but perhaps a transfer was possible.

    I think this woman was nutty, but certainly I would have laid out the risks (including the 6% risk of intracerebral hemorrhage) and then said: “In my opinion, course ‘x’ would be best” ER physicians, neurologists, and families shouldn’t think of a 3 (or even 4.5hour) window for IV-TPA, they should rather think that every minute counts. Each minute that passes makes the treatment less effective; that would be a better mindset.

    In your case, assuming there were no contra-indications, you could have said “The American Stroke Association recommends that TPA be given in these circumstances but this medication is controversial and I have my doubts about its benefit, so if it was my family member, I would decline.” I think this fulfills your role as a physician-expert – without taking away the ultimate decision from the family member.

    Perhaps you did in fact do this, and wrote your piece to highlight the craziness of this woman, but in case not, I suspect future cases will go more smoothly if you become more fatherly and advice-giving so family members may not have these complete breakdowns. (Despite what I’ve said, I have certainly had similar situations arise in which multiple family members are attempting to arrive at a consensus in an utterly confusing dialogue.)

  • Nuclear Fire

    Let’s not lecture people about their bedside manner. I think we can all assume a little creative license was used to emphasize the story.

    Prior to the expansion of the time cutoff to 4.5 hours, I was in a VA across the street from one of the major stroke centers. A gentleman had the witnessed onset of a stroke. For three hours we tried to get the poor guy tPA, but from nurses who refused to administer the medicine, pharmacists who had to be called in on a weekend, nurse managers claiming it was “against policy” to administer it on certain floors the drug never made it into the guy.

  • Dr. Grumpy

    The window HAS NOT been expanded to 4.5 hours. One study has suggested this could be done.

    The US FDA still maintains it at 3 hours as of present time.

  • Happy Hospitalist

    speaking of nursing refusing to “give the medicine”, I once had a patient in SVT that needed adenosine. The nurse refused to make the call to get it to the floor because that floor wasn’t allowed, even after I said I would push the darn med myself.

    I had to call an emergency response team to administer the medication. Perhaps I should have just called a code.

    Sometimes rules are contradictory to good care

  • Sam P

    I agree, I think Dr. Grumpy’s bedside manner was completely appropriate given the situation. Even assuming he wasn’t “fatherly” with these patients at all… it’s people like this I wouldn’t want to give any recommendation or opinion at all.
    Maybe I’m judging too quickly but the wife’s attitude seemed to me like that of someone who would be the first in line to misrepresent any advice offered and blame a doctor, and press a lawsuit if things went wrong.

    And Bob, I’m sorry for your loss, but Grumpy doesn’t deserve any of your venom. It’s clear he did take time to talk to the patient (more than once) and offer a clear choice. I’m sorry that wasn’t available to you, but I don’t understand why you’re unsympathetic towards him when it seems like he gave the patient’s family the opportunity that was unfortunately withheld from you.

  • Nuclear Fire

    Unless I’m reading the literature incorrectly, the 4.5 window is a Class 1, Level of Evidence B recommendation according to a scientific advisory from the AHA/ASA.

    (Disclaimer: my wife is one of the stroke docs with one of the authors of the advisory)

  • Mike

    tPA is not something that causes the patient to wake up 5 minutes later and walk out of the hospital. The benefits aren’t seen for like a year, and they are measures of physical therapy. So the odious person above with the sister who gets “watered through a tube” should stop acting like his sister missed out on 100 percent recovery.

    A stroke is a stroke. Its still the number 3 killer. Its still an awful disease. And we STILL can’t treat it very well. Bottom line is we need better drugs/treatment and prevention strategies.

  • cynical

    Genentech bought the AHA/ASA a new 10 million dollar building.

    Many of the tpa fanatics and promoters have financial influence from Genentech.

    NINDS was one positive study out of many failures. The extended window has been shown multiple times to cause harm. A similar analogy is If the Clippers beat the Lakers once then they must be better. No, that is why there is a whole season, a playoff, and a best of seven series.

    The posts illustrate the fanatic magical belief in tpa. This is not a magic bullet. This is not magic fairy dust.

    Dr. G. Sorry to hear you won’t be taking ER call anymore. Thanks to the medical-legal environment there is one less specialist to take care of you when you are critically ill.

  • AnnR

    Note to self: include coin-flip in Advanced Directives for indecisive spouse.

  • SarahW

    TpA certainly isn’t magic fairy dust. But what is more effective that removing the clot? Removing the clot can and does provide dramatic recoveries and long term improved outcome for stroke patients – why not inject into the clot in the wider window? Why not use the techniques that can retrieve the clot?

    Why not just lay it out, every second counts but the potential rewards must be weighed against the high risk?

  • evidence matters


    Sounds good, just like hope and chage does. Where are the results. What is the feasability. But scientific evidence does matter. Show published data with good studies. There is a handful of academic studies trying this. Where is the published results. How does that translate to general practice in community settings. there is not much published data because it is not good. Negetive studies don’t get published. This is one of the biggest errors in evidence based medicine (publication bias). Tpa is the biggest victim. The more people hope doesn’t make it true.

  • DocbLawg

    I have seen this case litigated. The patient comes in beyond the FDA approved 3 hour window and has a stroke hours later while an inpatient for observation. The Plaintiffs file a lawsuit and bring in a University based neurology expert who advocates for expanding the 3 hour window to 6 hours (all in theory of course). The Plaintiffs lose and have to pay a cost bill (the defense costs to litigate the case for this full jury trial) when it is all over.

    Just because Plaintiffs find that sterling expert in Academia who wishes that things were a certain way as concocted in his/her idealized mind it doesn’t mean that the real world docs in the trenches practice that way. In fact the specialty board for Emergency Medicine had issued an opinion on whether ER doctors should give adverse standard of care opinions against their peers on this issue once that 3 hour window is blown. That is why the Plaintiffs lost this case and that is why, as a patient, you get to the hospital at the first onset of symptoms of stroke.

    Just my opinion ~ DocbLawg

  • Mike Dudley

    My 50 year old Wife had a stroke while getting ready for work about 18 months ago. I called 911 and she was in the stroke clinic very quickly. Unfortunatly, the Neurologist recommended that they give her tPA to speed her recovery. Both her and I were scared and of course said yes to the treatment. She had improved from an 8 to a 4 and only 1 hour had passed. After they gave her the tPA, they sent her to critical care for obsevation. It’s a long story, but briefly, she was moving both arms and legs when she got the tPA and as the day progressed, I noticed she was getting worse. I kept telling the nurses she was getting worse. They said it was just the resut of her getting tired. Late that night I went home for a little sleep. Soon after I fell asleep, I was woke up by the police telling me that I need to get to the hospital, they need my consent to do emergency brain surgery on my wife. The tPA had cused her to bleed in her brain and the pressure was killing her. I made it there and the surgery to stop the bleeding was succesful. Now, after 18 long months of therapy, 500,000.00 dollars worth of medical bills and constant depression, crying, and the realization that our lives are over, my Wife is parilyzed on her left side, she has left side neglect, left side vision split, and short term memory problems. Because she got tPA, our lives have been ruined forever! I am sick of reading about how great tPA is! Check the facts. Many of the people that get tPA for stroke, recover no better than they would have without it, and it causes about 6 percent to bleed like my wife. Roughly half of the people that bleed die. My wife often says she wishes it would have killed her instead of having to live like this. It makes no sence for the doctor to ask for your consent to give tPA, you are most likely not even close to being qualified to make that decision, especially in the crtical and emotional situation you are in. It is absolutly agonizing for me to see my wife suffering like this. Except to help my wife dress, bath, eat, go to the bathroom, etc, I really feel like I have nothing to live for anymore. My grandchildren? Not really, the kids, like everyone else, avoid us whenever possible. I love my wife so much and, in my opinion, we had a perfect marrage. Now, not only have my wife and I lost everything that we had together in terms of our marrage. I lost my job. I worked for a small company that has a self insured health care benifit. Yes, the economy slowed down, but during the slow down, they implemented rotating layoffs. I was not part of that. My position was eliminated. In the last benefit meeting I attended, they showed the medical claims paid out for last year. Our claims were huge in comparison. I can’t prove anything, but I worked there for over 30 years and I know how things work around there. Recent new management has a very comprehensive profit plan and the CEO is always talking about health insurance. The slow down made it easier for them. The list of problems that tPA has caused goes on and on. Many in the health care system are quick to endorse this very expensive and highly controversial drug. However, when they destroy an entire family with a single dose, they are quick to turn their back on them while they reap the huge additional profits the resulting carnage has generated. They seem to be saying that because tPA has helped a few people, the total devistation that we have suffered is justified. If this had happened to their wife and their family, I believe they would have a much differnt opinion. I would never allow anyone I love to recieve tPA again, NEVER!

  • cynical


    I am so sorry. This promotion of tpa is one of the most flabbergasting things I have seen outside of undercover ACORN videos. I don’t know how? I don’t know why? Genentech money?? Neurologist zeal to want to try and treat a devastating disease?? The press for promoting some type of magic treatment??

    One neurologist in one of our community hospitals went gung ho on this initially and a third of the ICU became brain dead patients on vents.

    It is very hard for the truth to get traction. And in the meantime ER docs are getting sued on both treatment sides.

  • NW Hospitalist

    What I find most interesting in this discussion is that there is one post villifying the medical system for giving tPA and having a bad outcome and another for giving it and having a bad outcome.

    Medicine is just not so black and white, is it?

    We need more evidence that is free from bias (due to funding, statistical design, etc.) in order to make the best decisions. And we need to understand that nothing (except) death is 100% and that will NEVER know what would have happened had we made a different choice. Yes, the hemorrhage following tPA is terrible and I am sorry for your loss, but you don’t know that she would have had a better outcome without it. Maybe she would have survived at all. Everything is a calculated risk – and because it is the patient who is taking that calculated risk with their life, not the doctor – I think that it IS important to have them/family make that decision with the physician providing as much guidance as possible.

  • NW Hospitalist

    Should say:
    What I find most interesting in this discussion is that there is one post villifying the medical system for giving tPA and having a bad outcome and another for NOT giving it and having a bad outcome.

  • PharmNerd

    A few people have alluded to this, but it’s very important to lay out the risks & benefits of tPA to the patient/family. At our hospital, it’s myself, the neurologist, and the ED attending who are discussing the risks & benefits with the patients. So, the patient hears it multiple times – often from people with varying viewpoints on the drug’s actual validity (much like you see in these comments).

    What I say, in a nutshell: 1 in 3 chance that tPA will probably make you better 3 months down the road. This improvement probably won’t be immediate, and may not be particularly dramatic.

    1 in 20 chance that tPA will result in a symptomatic bleed, and you’re worse off (potentially dead). And that’s for the “perfect” patient. Older patients with worse symptoms, for example, probably have quite a bit higher chance of bleed — a risk that’s difficult to predict.

    No matter the risk or how serious it’s described to be, patients/family often come to the decision that “I’d rather be dead than live like this, so give the drug.” Explaining that the symptoms could possibly improve over time, even without tPA, rarely dissuades them.

  • Mike Dudley

    NW Hospitalist,
    Thanks for demonstrating my comments. A conscientious reader would understand that I am not “vilifying the medical system for giving tPA and having a bad outcome” By the way, if your family’s future hopes and dreams had been swept away, you were financially ruined, and you had to watch your spouse suffer every day until one of you dies, I doubt that you would describe this as simply a “bad outcome”
    I am however vilifying the medical system for giving tPA, having a “bad outcome”, and turning their back on the family they destroyed.
    A conscientious reader would have noticed that I said “She had improved from an 8 to a 4 and only 1 hour had passed.” and realized that she was quickly improving on her own. Dear God, I wish we had heard PharmNerd’s description of the very real risks vs. the marginally possible benefits!

    NW Hospitalist, you seem to say that what happened to us is justified because the medical system is trying to get “more evidence that is free from bias”. Well, we are not lab rats. However, they don’t generate additional profits by destroying lab rats.(sarcasm rooted in the truth)
    You said “because it is the patient who is taking that calculated risk with their life, not the doctor – I think that it IS important to have them/family make that decision” WTF? Come on, how often does a patient come into the ER medically qualified to make that decision? Oh yea, and then there is the stroke thing going on as well. Give me a break! According to you, there isn’t enough data for a neurologist unaffected by family attachment to make that decision.

    Most days I ask myself, how will we get through this day? Then I realize that I am 53 and my wife is 51. We could potentially have to live like this for another twenty or thirty years. Then I pray that we both die long before that.

  • cynical


    Your situation is tragic. Every doc that administers TPA have to read your story.

    Aside, the evidence is not clear. The family/patient has to decide. How can it be any other way? The doc can’t predict the outcome for the patient. But the situation sucks. Very very smart people that study this for a living will disagree. My bias would be to never give it and let the outcome be what it is. In your case, If there was any hint of spontaneous improvement I would use that as an excuse to dismiss TPA asa treatment. option.

    I agree with the pharmacist above. Many, in the fire of the moment, side with the “walk or die” philosophy.

  • Dr. Grumpy

    If the patient is improving, they do not qualify for TPA.

  • Hemdoc

    I plan to have “give me tpa if I stroke” tattooed on my forehead. I am not interested in being paralyzed; I prefer to get better or die. By the same token, I have made it clear to my family (yes, I have a living will) that, although I like vegetables, I don’t plan to be one, if a bleed leaves me marginally alive. It sure would have helped Dr. Grumpy’s disposition if his patient had made his wishes known before he couldn’t talk — I try to advise all my patients to do so.

  • Mike Dudley

    You are aware of the considerable risks and limited success when tPA is used, before the intense emergency room/stroke situation. If tPA is still a gamble you’re willing to take, good for you. Frankly, I really hope you never have to worry about it. However, most people do not have that information until they are in an atmosphere that makes it impossible for them to make a rational decision. Maybe if just some of the recourses used to inform the public about the scourge of ED were dedicated to distributing this critical information, more people could have your knowledge when they need it.

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