This is a big and important topic but still a little bit confusing to say the least.
The way I want to view the world is like this.
PE is not a single disease but instead something we should call by different names.
- these are the tiny sub segmental PEs that we diagnose because diagnostic protocols bend our arms and force us to become bad doctors and it’s not our fault… These PEs get 3 or 6 months anticoagulation and we cross our fingers and hope they don’t die from the anticoagulation.
2) The thrombus of death
- these are the sickish looking people whom you are actually worries about and have high clot burdens and strainy looking hearts and ECGs. These PEs are the ones you think about giving the drug of the big pharma devil to – tPA.
In my imaginary rose tinted world, fluff gets no treatment and the thrombus of death gets tPA.
The problem is that the reality is a whole lot more complicated than that. There is good reason that we treat the small PEs just like the bigger ones. We simply don’t know if they’re dangerous or not so we err on the side of “if in doubt treat” (despite the fact that the evidence for anti-coagulating any PEs is a little ropey)
This paper suggests that these small PEs might be more dangerous than I’d like to believe. [Hat tip to EMU for making me aware of this]
Exter den PL, van Es J, Klok FA, Kroft LJ, Kruip MJHA, Kamphuisen PW, et al. Risk profile and clinical outcome of symptomatic subsegmental acute pulmonary embolism. Blood. 2013 Aug 15;122(7):1144–9. [Full Text Link]
- data from 2 prior observational diagnostic studies, one was the Christopher study, the other was much smaller. Both European
- as a result the data is only as good as the original studies which in this case should have been pretty good
- death where PE could not be ruled out as a cause were considered recurrent PE. Not great but probably the best way to do it.
- logistic regression used to see if there was an association between where the PE was and the outcomes
- 3800 pts, 2700 of which got CTPA
- 21% had PE overall.
- 115 people with isolated Sub Segmental PE (SSPE)
- they appeared similar to those with more proximal PEs (except for Wells scores, where they tended to be lower)
- 3 month follow up was better than 99%
- 4/115 developed VTE in 3 month follow up. the numbers come out at 3.6% v 2.5% suggesting recurrent VTE more likely in the small PEs!
- of note those in whom PE was ruled out developed VTE 0.8% of the time
- I’d love to know the details of the 4 people who developed recurrent VTE in the SSPE group but they don’t tell us
- the mortality numbers are quite high 10% for SSPE, 6.3% for more proximal PE and 5% for those in whom it was ruled out. This seems very high. 1 in 20 who had a negative work up for PE were dead in 3 months?
- this seems like a very sick population where 1 in 20 of those with a -ve PE work up were dead in 3 months
- the numbers with SSPE here are very small (115)compared to the overall numbers and therefore the number of people for whom the outcome of interest occurred (recurrent VTE or death) was absolutely tiny.
- Everyone in this study was treated which we are assuming is an effective treatment. Therefore this study tells us the natural history of treated SSPEs. It would be really nice to know what the natural history of untreated SSPEs is.
Ryan over at EMLitofnote has reviewed the paper too.
Mattia Quarta of EMPills fame has this to say:
Dear Andy thanks for sharing your thoughts on this paper.
One thing I’ve noticed is that the prevalence of SSPE between the two cohorts that were merged for this study seems pretty different. In the Christopher study 110 SSPE were found which means that only 6 come from Klok publication.
So it’s more less 17% vs 5%. Apparently the two cohorts are not so homogenous after all.
In the Christopher study as opposed to Klok PE level determination apparently was not specifically planned. All 41 PEs excluded because localization was not reported belong to the Christopher study.
Klok and colleagues adopted a specific strategy to locate the level of the clots found. So I wonder whether Cristhopher data are completely reliable when it comes to PE level, considering that a certain grade of variability exists between radiologists in the interpretation of subsegmental clots. With these numbers even one patient can make a huge difference in the results.
I’m not really sure this study will change my point of view on SSPE. For the moment I still lean toward the same imaginary rose tinted idea that fluff gets no treatment unless they have DVT.
I’ll wait until we have more data. http://clinicaltrials.gov/show/NCT01455818