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Welcome back to the tasty morsels of critical care podcast.
TTP is a lovely ICU diagnosis. Not so much for the patient but it’s one of those ones that is niche enough to not have been picked up via the usual filters of ED, medical team to the ward. There is a definitely a chance to shine and make the diagnosis.
This is form of MAHA (microangiopathic haemolytic anaemia). Best to avoid detail on what these are for now but suffice to say some of them are very ICU relevant and the ket feature will be something called schistocytes which are found on the blood film that you haven’t ordered yet but definitely will next time you see something like this.
The pathophysiology involves something in an autoimmune sense getting all excited and reduces the levels of your favourite ADAMSTS13. ADAMSTS13 is a mouthful of an acronym that you would hope was named after Dr Adams with a few letters added on but is in actual fact a mouthful of an acronym abbreviating an even more ugly sentence worthy protease called “a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13”.
The trigger for your body attacking the unfortunately named protease is useful some kind of stressful event like surgery, trauma or some nasty infection.
In normal circumstances ADAMSTS13 is there to stop your platelets and your vWF getting two cosy in these things called multimers. When the ADAMSTS13 disappears then all your platelets disappear and you start clogging up small vessels with these big multimer thingies. TTP is therfore a form of TMA (or thrombotic microangiopathic anaemia). This “TTP for dummies” level explanation is enough to suggest the clinical features…
Which are:
- some funny neuro things inc seizures
- a rashy petechial thing
- an AKI
- a profound, “no joking around” thromboyctopaenia
- fever is common
There is a “PLASMIC” score that can be used as a diagnostic tool where you score points for certain features and we all know that points mean plasmapheresis in this game. I have never used the score but it is a thing.
Ultimately you will need your ADAMSTS13 to seal the diagnosis which will be nice when it comes back 4 days after you’ve already started treatment.
And this is key. Treatment should be started based on suspicion. Low platelets and a MAHA with maybe an AKI may well be all you need to start treating this. If you don’t then mortality is in the 90% range.
Treatment consists of:
- PLEX – actual proper PLEX with plasma replacement as opposed to just washing out all the good stuff and giving albumin as replacement. The plasma replacement replaces factors and reduces the bleeding risk (which is already high) but also acts as a source of ADAMSTS13. This is believe it or not an intervention actually supported by an RCT back in 1991 of just over 100 patients.
- Some kind of immune suppression to stop the production of autoantibodies that are wiping out the ADAMSTS13
- steroids commonly used
- rituximab can be used
Giving platelets is poor form generally with people objecting on the basis of “fanning the flame” type arguments which sounds very reasonable. Theoretically giving them FFP while waiting on PLEX seems like it might be sensible but in reality probably does nothing when the autoantibodies are still around.
UPDATE:
Caplacizumab is a new drug with now 2 RCTs supporting its use and is finding an increasing role, early in the role of TTP, even immediately after PLEX is started. Some suggestion it might even replace PLEX.
References:
- Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, Spasoff RA. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med. 1991 Aug 8;325(6):393-7. doi: 10.1056/NEJM199108083250604. PMID: 2062330.
- Deranged Physiology
- Tasty Morsels of EM 070
- https://emergencymedicineireland.com/tasty-morsels-em-070-ttp/