Podcast # 51: Fibrinolysis in Pulmonary Embolism

Update: A more current review of this topic can be found in podcast 128

Jeff Kline is the master of all things pulmonary embolism in emergency medicine. This is a lecture he gave on fibrinolysis for pulmonary embolism. He discusses both massive and sub-massive PE.

Here is a pdf of the slides.

If you haven’t already, you should also check out the AHA PE guidelines. I have a summary and the diagrams in another post.

Fibrinolysis in Pulmonary Embolism with Dr. Jeff Kline

The lecture starts with a few non-fibrinolytic points:

  • Use PERC with clinical gestalt
  • You can use a high-senstivity d-dimer in ALL risk groups
  • Use a d-dimer with elevated cut-offs based on trimester in pregnant patients
  • A high-sensitivity CTPA is the best thing we have and a negative is negative for all risk groups

Feel free to discuss any of those in the comments

Massive PE

In the guidelines, the definition is PE with SBP < 90 for > 15 minutes

Dr. Kline basically says that if you have an SBP < 90 at any point, the patient MUST be given fibrinolysis or you better have a good reason why on your chart.

Sub-Massive PE

Here are the points Dr. Kline can state definitively:
After lytics,

  • The patient will feel better
  • The clot will resolve more quickly
  • There will be no increase in serious bleeding (Note in the original study, 2 patients with pre-lytic ICH were coded as complications)

What he can’t say yet (but he has the largest RCT going on now) is mortality reduction

So who does he think should get lytics in sub-massive PE?

  • BNP >90 or Pro-BNP >900 elevation (he states BNP is his go to marker). SENSITIVE
  • Troponin positive SPECIFIC
  • Echo with RV dysfunction, hypokinesis, dilation

He also states a low room air pulse ox is an indicator of needing lytics.

Choice of Drugs

Alteplase-he continues heparin during the infusion. He also feels you can just give the 100 mg as a bolus if you need to.

Tenecteplase-this is what he would want to receive if he had a PE. He gives it simultaneously with LMWH.

Mentions that lytics don’t destroy all of the clot they just chew away at the big ones a bit.


For more PE stuff see the diagnosis protocol post and the PE debate insanity.


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  1. Brian says

    How do you, and Dr Kline, if he’s out there, feel about lytics when the patient presents w/ syncope, in the absence of current hypotension or clinical shock?

    • Zach says

      Or even lytics during a cardiac arrest wiht a high index of suspision of PE? Such as a recent long bone fracture?

      • says

        TROICA, which is what the AHA based their no-lytics in undifferentiated cardiac arrest stance on, excluded pts in whom the clinician had a strong suspicion for PE. So if you have a strong suspicion, then you should probably lyse.

  2. Carlos Basaure says

    In patients with diagnosis of PE that are at arrest (non shockeable) and don’t get rythm back, can you use lytics during CPR?, You need to use infusion or bolus administration in the case that you don’t have tenecteplase ?

    • says

      if you have already diagnosed PE and they arrest, definitely lyse unless contra-indications (and they would have to be pretty STRONG contra-indications). If you only have alteplase give all 100 mg as a push during arrest as per Dr. Kline.

  3. Mike Jasumback says

    Holy Crap Weingart/Kline! YGBFSM!

    OK, I’m only 15 minute in and already my head is going to explode! Lytics for pretty much any submassive PE without a good reason? I’ll give you a good reason, NO GOOD PUBLISHED DATA TO SUPPORT A MORTALITY BENEFIT AND A 1% CHANCE OF ICH! How’s that for a good reason? How bout the fact that Kline’s definition and the recommendations of AHA and everyone else doesn’t support that aggressive of treatment.

    Allright Rant over. Kline is probably right. I lyse these folks too. But I do it fully realizing that there is no solid data to support me……Yet.

    So my concern really is not the therapy, but the presentation. The unwary could get themselves into trouble with this one. Kline does not define the standard of care (maybe he should) but blind reference to his authority could get us all in deep doo-doo!

    Mike J.

    by the way, I think Kline is brilliant and clearly knows more than me about PE and its DX and TX, but I’ve been burned by that kinda stuff before. Anybody remember things like Hyperventilation for Head Injury, Steroid for Spinal Cord Injury, Lasix for CHF, Theophylline for Acute Asthma etc, etc……

  4. says

    For anyone not of the net generation, YGBFSM can’t be spelled out on my family oriented blog : )

    I think Dr. Kline was fairly clear that he doesn’t have evidence of mortality benefit for submassive. Though he is actively engaged in creating it right now.

    I think until that comes out, you can tell your patient that their chance of being a cardiac cripple is dramatically decreased with lytics. I think even the 1% is an overestimation of the ICH risk given the data he presented, but I think it is a fair number to use for consent. Then let your pt decide.

    Dr. Kline doesn’t define standard of care, but in some ways AHA guidelines do. I think those guidelines do give enough latitude to go on your clinical judgment.

  5. Josh E says

    d-dimer testing is an interest of mine and I’ve been unable to find conclusive evidence that d-dimer testing is warranted in pretest probability high risk patients. mainly, all of the studies I’ve found show that d-dimer is highly sensitive, but fail to achieve statistical significance because of insufficient power. Is there data to support Kline’s statement regarding d-dimer use in high risk patients? is my fear to use it based only on theoretical Bayesian analysis?

    • zohaer says

      would like to know .. in a high risk pt for PE , would you send that pt home without CTPA if the high sensitive quantitative D dimer came back negative * and pt is not on anti coagulated and presents within 24 hrs of PE symptoms ?

  6. luffy says

    Hi Dr. Weingart :)

    Love your blog and your sense of humor! Cannot wait to hear you speak at the AllNYC conference next Wednesday!

    Anyway, I’m curious to know what you think about this one: 80yo patient hypotensive, tachycardic, and tachypneic, sats in mid 80s. History of cancer with mets s/p chemo. Also febrile and neutropenic. He was given tPA early for suspected PE; no d-dimers, no imaging or u/s, no other workup. The ICU team was raging that the ED team didn’t consider anything else in the differential of hypotension/tachypnea and that he wasn’t even blue in the face/at death’s door yet (pt was not intubated either, I think he was DNI) and there was no imaging done first and they could do no abg’s or other blood draws because of the 24h tPA window. The ICU attending was pissed off as hell lol and 80% of rounds was him talking about how retarded this workup was. How would you approach this kind of patient?

    (The pt turned out to have a left pop DVT and died a few days later, probably 2/2 overwhelming pseudomonas sepsis or malignancy.)

  7. PB says

    Dr Weingart LOVE your blog. Amazing stuff. I’m a EM resident in NYC area. Listened to this post this week (I’m a little behind). I dug around to find some of the references mentioned in the lecture and thought I would post the links:

    The “old” PE studies showing high mortality:
    MAPPET registry: http://www.ncbi.nlm.nih.gov/pubmed?term=9264496
    ICOPER: http://www.ncbi.nlm.nih.gov/pubmed/10227218

    The “newer” PE studies showing lower mortality:
    EMPEROR: http://www.ncbi.nlm.nih.gov/pubmed/21292129
    HCUP: http://www.hcup-us.ahrq.gov/nisoverview.jsp (not really an article)

    Also here is the AHA statement on PE. Figure 6 references these same studies: http://circ.ahajournals.org/content/123/16/1788.full#content-block

  8. Mike Wickham says

    Had a moderate pre-test prob for a DVT, D-Dimer + but US negative pt who was therefore not anticoagulated throw a saddle emblous a week later. This has reminded me of ensuring follow-up US in a week or so in my moderate to high pre-test probs. What is your take on this? Jeff Kline’s?


  9. James Hildebrand says

    Hi Scott-I’m a pgy3 EM resident starting to think about how I will choose to manage my patients next year without an attending safety net. I’ve been catching up on old episodes, great stuff as always. Like Josh above I would love it if Dr. Kline had a resource or reasoning for why he trusts D-Dimer in all risk levels. A quick bit of googling found me this


    But does he have more info with a more inclusive pt group? Also, what elevated cutoff does he (or you) use in pregnancy? Citation?


  10. Stefan says

    So maybe I missed it in the lecture, but what was his advice regarding whether or not to give a heparin bolus before putting the patient on a gtt? Also, would you start them on the heparin and then give the tPA, or the other way round (or does it even matter)?

  11. Dan Richardson, D.O., FACEP says

    Can you provide the reference for D-dime level in pregnancy. What level is acceptable for each trimester. I know I have heard this on your site or EMRAP but need to educate myself as well as my OB!! Thanks.

  12. Michael Grubbs says

    Enjoy the podcast! I am a hospitalist in a community hospital who enjoys interacting with the ED and ICU. I am often amused by the difference in the approach the two groups will take to the same critical patient.
    Would you or Dr Kline thrombolyse an patient with a Cr of 2.4, precluding CT angio, with a high clinical suspicion of PE, hypoxia, elevated and rising troponin and significant RV dysfunction on ECHO?

    • says

      can’t speak for Kline, but first I would do a bedside dvt ultrasound. If negative, I would prob. CT the pt anyway before lysing. If the pt started to drop their blood pressure and there were no contra-indications, I would start talking to the pt about blind lysis.

  13. Mn says

    Hello, I am a hospitalist. Do you have a feeling on giving tpa to patients who already received lovenox before the diagnosis was confirmed only to then become unstable. I have done this one time mainly because my patient was dying and I had no other choices. She blew 4 intrabdominal hematomas but was discharged to home alive for Christmas. How do you handle that situation. We have lovenox and late please as our drugs.

    I had another case where my colleague planned to administer tpa to an unconfirmed case of pe. We stopped and completed the ct quick instead. The diagnosis was hemorrhagic pericardial effusion with tamponade. Another tpa lesson I won’t forget.

    My third memorable tpa story was on a stroke patient, who immediately got angioedema from the tpa and needed urgent intubation. Even though a stroke case, relevant to tpa use.

    Love the info and passion. Thanks!

    • says

      Jeff gives lovenox simul. with tenecteplase so I would have no problem giving tenecteplase to these patients. I try to get imaging before giving the lytics in a patient who is not coding if at all possible, for just the reason you mention. If bedside dvt ultrasound is positive, then I think that is enough in the proper clinical scenario.

  14. Charles Tran says

    Hey Scott,

    Give 100 mg during a cardiac arrest as a push? I agree but I wanted to make sure I read that right.

  15. Krystle says

    Would you give lyrics in patients with massive PE and pulmonary infarct?? I cannot seem to find any literature about this other than it is not listed as a current contra-indication

  16. David says

    Hey Scott,

    Thought it would be a good time to revive this topic with 2 new trials out (TOPCOAT and PEITHO)

    IM/EM/CC doc here (finishing cc fellowship now). Enjoyed hearing Kline’s viewpoint, although based on the recently published TOPCOAT and PEITHO trials I disagree with them. I 100% believe lytics reduces RV dysfunction and pHTN in the long-term. However, nobody has been able to show this results in a patient-oriented benefit (improved quality of life). The topcoat trial looked promising but Kline terminated it early for logistical reasons so left this question largely unanswered. The PEITHO trial (in my opinion) just demonstrated giving everyone lytics upfront prevents you from having to give a minority of patients lytics later. We also know from the PEITHO trial that the risk of ICH and major bleeding is NNH 15 and 56, respectively. I find it hard to justify giving lytics to stable patients with these NNHs when there is no mortality benefit, no reduction in recurrent VTE and frankly no patient oriented benefit (quality of life??). I suspect lytics may actually reduce long-term heart failure symptoms. We need good data to demonstrate this, and to tell us who exactly would benefit and how much they would benefit. Until that day arrives I find the lytic risk/benefit ratio unfavorable.


  17. Dawn says

    I have a question about dosing. I have not found a clear consensus about dose to give. From what i understand, it is 50mg-100mg; but is this over 1 hour, 2 hour? Some say give 50 mg over 15 minutes and some give 100mg bolus. It’s confusing. Are the doses the same for ALL massive PE’s (cardiac arrest vs. non-arrest patients) or is there a difference?



  1. […] the data, I would now want lytics for my submassive PE. (Here is a link to a great talk by Mr. PE Jeff Kline. where he talks about his treatment […]

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