Welcome back to the tasty morsels of critical care podcast.
Plasmapheresis (or PLEX) is one of the machines we tend not to have responsibility for in the ICU. Unlike CRRT we tend to defer to another specialty to do this. As a result we don’t need to know the same level of detail we need for CRRT, however we do need to know the basics and in particular where it might be indicated (and indeed where it isn’t).
Up front there are some problems with the terminology
- Plasmapheresis = process of removing plasma from the blood.
- Therapeutic plasma exchange = removal of the plasma (plasmapheresis) followed by replacement with something else (can be clean, frersh plasma or albumin or even crystalloid)
Plasmapheresis is another of those therapies that comes with a tremendously compelling physiological narrative where we can rid the blood of evil humours. We do something similar with CRRT, washing the blood of the nasty small particles and restoring electrolytic stability. With plasmapheresis the washing is much more extensive with removal of all the non cellular components of the blood.
Some good examples of pathological things removed during plasmapheresis include
- toxic antibodies
- immune complexes
It is a rather blunt tool given that you’re removing all of the circulating plasma, removing known toxins and unknown toxins but also some important things like all of your albumin, clotting factors and all the other known components of the plasma. We can replace these things fairly easily and the body will of course continue to produce all the normal components of the plasma and indeed the abnormal bits that you were trying to remove in the first place with plasmapheresis. It’s a bit like turning the immune system on and off again. Turning it off gets rid of all the circulating badness but when you turn it on again and click that spam link in your email then the whole cycle of badness begins again.
Which is why plasmapheresis is spectacularly unhelpful on its own without some kind of a chaser of immunosuppression. That could be steroids, or a dose of everyone’s favourite mab and CD20 blocker, rituximab or one of the profound immune system bullies like ciclophosphamide.
Oh’s textbook has a box listing the established indications and splits them up as follows:
- Immunoproliferative disease with lots of immmunoglobulin production like
- hyperviscosity syndrome
- myeloma with AKI
- Autoimmune diseases with autoantibodies or immune complexes
- Catastrophic antiphospholipid syndrome
- some paraneoplastic diseases
- some of the autoimmune encephalitides
Of note ANCA +ve vasculitides have typically been treated with PLEX but the recently published PEXIVAS trial would suggest there’s no great benefit. This has been a trend in most of the literature, particularly when PLEX is compared with something like IVIG, the outcomes tend to be similar. Indeed guidance would suggest for something like GBS that you use IVIG or PLEX but not both. For revision purposes you can somewhat conflate your list of indications for IVIG and PLEX.
In practice it is not unusual to see IVIG being given (as the less invasive option) followed a week later by PLEX because the IVIG didn’t have an effect. As Adam Thomas notes on the IBCC podcast that there is definitely a bit of a face palm moment as all the pricy IVIG you’ve just infused is removed by the plasmapheresis.
A few other points
- removal of IgM easier as it’s 75% intravascular and one or two runs of plasmapheresis is enough to clear it. IgG is much trickier as lots of it is outside the vascular compartment so it drops during plasmapheresis then goes up again as it redistributes. This requires several runs and immunosuppression to get it all gone
- citrate is generally the anticoagulant of choice for the circuit and if you’re replacing with plasma (rather than albumin) then remember that plasma has a high citrate content also
- most of the time albumin replacement is all that is needed as the liver will rapidly replete the coagulation factors. The major ICU exception to this is TTP where they are so bleedy already that depleting their coagulation factors just might be the straw that broke the camels back or indeed the absence of factor which broke the tenuous platelet plug.
Padmanabhan A, Connelly-Smith L, Aqui N, Balogun RA, Klingel R, Meyer E, Pham HP, Schneiderman J, Witt V, Wu Y, Zantek ND, Dunbar NM, Schwartz GEJ. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019 Jun;34(3):171-354. doi: 10.1002/jca.21705. PMID: 31180581.
Walsh M, Merkel PA, Peh CA, Szpirt WM, Puéchal X, Fujimoto S, Hawley CM, Khalidi N, Floßmann O, Wald R, Girard LP, Levin A, Gregorini G, Harper L, Clark WF, Pagnoux C, Specks U, Smyth L, Tesar V, Ito-Ihara T, de Zoysa JR, Szczeklik W, Flores-Suárez LF, Carette S, Guillevin L, Pusey CD, Casian AL, Brezina B, Mazzetti A, McAlear CA, Broadhurst E, Reidlinger D, Mehta S, Ives N, Jayne DRW; PEXIVAS Investigators. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. N Engl J Med. 2020 Feb 13;382(7):622-631. doi: 10.1056/NEJMoa1803537. PMID: 32053298.