We are used to giving full-dose thrombolytics for massive PE and half dose or an interventional procedure for high-risk submassive, but what if there was an easier and safer way? This paper is the beginning of a path to creating a less resource intensive effective strategy to resolve the hemodynamic perturbations of sick pulmonary embolism patients.
The Paper
Reduced-Dose Systemic Fibrinolysis in Massive Pulmonary Embolism: A Pilot Study
Summary
P: 37 Adult patients with massive PE (PE on CT requiring vasopressors) excluding pts with standard tPA bleeding exclusions. Had pre/post echo.
I: t-PA 25 mg IV over 6 hours (may be repeated x 1 if hemodynamic instability continued, but no pt required this). Heparin 70 unit/kg bolus followed by 1000 unit/hr started after completion of tPA
Success defined as clinical improvement of symptoms, restoration of stable hemodynamic status, along with 3 echo criteria without death/major complications (ischemic stroke, intracranial hemorrhage, embolism (coronary or peripheral), bleeding requiring transfusion). Actual primary endpoints were in-hospital mortality, major complications, development of PH, and right ventricular distension. Secondary endpoints were 6-month: mortality, PH, RV dysfunction. All pts were followed for 6 months
O: All pts became hemodynamically stable. Troponins decreased. Echo markers got better. 18 patients (56.3%) underwent repeat pulmonary CT angiography 24 hours after the TT. Of these 18 patients, total lysis of the thrombus was observed in 16 patients (88.9%) and the remaining two patients had >75% lysis of the thrombus.
No major bleeding events were observed. Three patients had minor bleeding, two patients had epistaxis and the remaining patient had gingival bleeding. The two episodes of epistaxis were observed 2 days after TT and gingival bleeding was observed 3 days after the TT
Additional Points
Xa Monitoring seems like a boon but may be less informative post-fibrinolytics
PTT encompasses the effects of tPA while Xa may not, perhaps regress to PTT in post-fibrinolytics patients
Get Access Lines before Fibrinolytics
A line in common femoral artery and vein can save your and your patient's butt later on down the line
Additional New Information
- Thromb Res . 2014 Mar;133(3):357-63. doi: 10.1016/j.thromres.2013.12.026. Epub 2013 Dec 23. Lower dosage of recombinant tissue-type plasminogen activator (rt-PA) in the treatment of acute pulmonary embolism: a systematic review and meta-analysis
Conclusion is that lower doses are as effective with markedly less bleeding - Multi-center retrospective propensity matched showed less complications but same efficacy with reduced dose
More on EMCrit
- EMCrit Wee – PERT Redux Panel Discussion
- EMCrit 308 – Risk Stratification and Treatment of Pulmonary Embolism (PE) 2021 – Is the PERT Wilted?
- Submassive & Massive PE
Additional Resources
Professor
Nassau University Medical Center
No conflicts of interest (coi).
- EMCrit 385 – Eye Trauma I – Retrobulbar Hematoma, Orbital Compartment Syndrome, and Paracanthal Decompressions - October 5, 2024
- EMCrit Wee – Did this Really Just HAPPEN? – The HAPPEN Trial Hot Take – NIPPV for COPD - September 29, 2024
- EMCrit 384 – The Vascular Guy on Vascular Access - September 23, 2024
Reduced dose thrombolysis with 25 mg TPA has been my practice for nearly 20 years. I give 10 mg over 10 minutes and the remainder over 2 hours. I have had no issues with bleeding and have only had to redose 1 person with another 25 mg. As has been pointed out by others the pulmonary circulation receives the entire dose of thrombolytic giving a strong rationale for a reduced dose. My shop switching to TNK for stroke next month. Need to figure out the equivalent dose.
This pilot study is promoting use of 25 mg alteplase (1/4 of 100 mg full-dose). One previous retrospective study of 1/2 dose (50mg) alteplase suggested escalation needed more often. [Half-Dose Versus Full-Dose Alteplase for Treatment of Pulmonary Embolism. Kiser TH, et al. Crit Care Med. 2018;46(10):1617.] Another retrospective 1/2 (50mg) alteplase study suggested similar reduction in PASAP, RV/LV ratio but with better cost and duration of hospitalization than catheter directed thrombolysis. [Retrospective comparison of ultrasound facilitated catheter-directed thrombolysis and systemically administered half-dose thrombolysis in treatment of pulmonary embolism. Sharifi M, et. al. Vasc Med. 2019;24(2):103. Epub 2019 Mar 5.] One… Read more »
thanks for the citations, Scott! I would love to see something like 1/4 dose TNK study, but it does have some disadvantages as once it is in, it is in, no takesie backsies as opposed to a continuous infusion like you would get for alteplase. study I’d really like to see is full dose TNK vs. new AIS dose TNK for crashing massive PE. You can cross the pt to full if no improvement in 10-20 minutes or something similar. My contention is the reason that new AIS dose did better than STEMI dose is that we are dosing all… Read more »
Loved the discussion. Just a thought with TNK versus tPA especially in PE (PE is not time specific so we are not really sure about chronicity of the clot and based on the stroke data that tPA or tNK doesnt work well if the clot is subacute or chronic). I guess once you are commited to give TNK or tPA so there is no going back for me hence TNK makes sense and theoretically should have less bleeding risk. Another question which I have – When and how do you start Heparin (some center follow Fibrinogen level or TEG etc… Read more »
Scott. Can you help me understand why we in medicine are not, or maybe I’m wrong and someone is, looking at this (Systemic Peripheral Fibrinolysis) in weight base dosing (mg/kg). Currently we dose thrombotic strokes weight base with the trending to lower doses but with cardiac and PE we are giving the same non-weight based dose to a 60 kg small lady as we are a 150kg advanced BMI say male?
Fantastic episode Scott! This is an brilliant paper that I think will be a key gateway to the future of thrombolysis in PE. 100mg over 2hrs dose for Massive PE has always seemed way too high– completely made up “nice round dose”….. just like 1mg Epinephrine for cardiac arrest. 🙂 I’ve been a proponent over the years of half dose tPA (50mg Alteplase over 2 hrs). Although MOPETT was looking for long term outcomes I do think it showed safety and made a lot of sense to me for patients acutely in trouble. You mentioned several times 50mg over 1… Read more »