Plasmapheresis
Plasma exchange
Dose: Rescue therapy: 3-5 exchanges usually QOD; maintenance therapy: regimens not standardized.
Onset of action: 1-2 wk
Adverse events: Vascular catheter-related complications: infection, thrombosis, pain, blood loss, hypotension, and hypocalcemia.
Monitoring parameters: Baseline vital signs and during the procedure; CBC and BMP; fibrinogen and calcium before the next exchange when performed in the acute setting daily or QOD.
Avoid ACE-I 24 hours prior to plasmapheresis.
Plasmapheresis is established as a major therapeutic option for acute management, disease stabilization, and, rarely, long-term disease maintenance in otherwise treatment-refractory patients. Major indications to date are in the acute phase of GBS, and for critical worsening or stabilization in patients with CIDP and MG—although all these indications remain off label.
Current technology involves the use of a continuous-flow apheresis machine. The device selectively exchanges the plasma portion of blood, most commonly with a diluted albumin solution, before returning the cellular components of blood in the intravascular space. Plasma exchange removes normal antibodies and pathogenic autoantibodies, complement protein, immune complexes, and other nonspecific immune mediators. A study of PLEX in MG patients treated for exacerbation showed that the maximum decrease in total IgG and acetylcholine receptor antibody levels (about a 60%–70% reduction) occurred on the last day of a five- or six-procedure course of PLEX. A slow increase of normal and pathogenic antibody levels started after the completion of PLEX therapy. By week 5 after PLEX initiation, antibody levels remained 20% below baseline levels.
PLEX has been perceived as a complex treatment that requires central venous access and usually a hospital admission. However, data from centers with clinical volume and accumulated experience indicate that PLEX is generally well tolerated, and also that it can be consistently and successfully administered via peripheral venous access. For GBS or MG crisis, PLEX can be administered daily or every other day. However, some PLEX experts prefer every other day or longer intervals to allow clotting factors to return to the normal range. PLEX is best studied and has the strongest evidence in GBS. Landmark randomized studies in the 1980s established that PLEX accelerates improvement compared with supportive care in GBS. PLEX is probably effective for mild GBS and should be considered for use in this patient population as well.
PLEX is effective for short-term management of CIDP, typically as an adjunct to other oral immunosuppression. For neuropathies associated with monoclonal gammopathy of undetermined significance (MGUS), PLEX was shown to be effective in the short term, in particular for IgG and IgA MGUS-associated neuropathy, whereas IgM MGUS is increasingly considered a separate nosological category.
There has been no adequate randomized trial demonstrating that PLEX is effective in the management of MG. This was underscored in a 2011 American Academy of Neurology plasmapheresis practice guideline that cited “insufficient evidence to support or refute the use of PLEX for myasthenia gravis.” However, PLEX is widely accepted as one of the cardinal therapies for MG, and, in fact, is reserved for some of the most severely affected patients. Specifically, it is used for MG crisis, worsening disease while oral immunosuppression is augmented, prior to thymectomy in patients with respiratory or bulbar impairment, and less commonly for maintenance in treatment resistant cases (although no specific treatment protocol has been systematically evaluated). As mentioned previously, the clinical evidence for PLEX use in MG comes from studies showing, first, a benefit from IVIG, and, second, the comparable benefit from IVIG and PLEX in comparative effectiveness trials. Muscle-specific kinase (MuSK) antibody–positive MG patients appear to respond very well to PLEX. Retrospective studies of cohorts in Italy and the United States indicate a likelihood of a favorable response ranging from 51% to 93%.
In general, 1 to 1.5 plasma volumes are exchanged per PLEX procedure. This balances target plasma macromolecule removal, on the one hand, with procedure time, tolerability, and cost, on the other.