Therapeutic Plasma Exchange

Therapeutic plasma exchange (TPE) is a procedure in which whole blood of the patient is passed through an apheresis device, which separates and removes plasma. Other components are returned to the patient together with replacement fluid.

Pathophysiology

TPE is used to treat diseases that are thought to be caused by a substance in plasma whose removal can help with disease resolution. TPE is mostly used for antibody (and rarely immune complex) removal from circulation. It can be used to remove other molecules, such as drugs, paraproteins, and low-density lipoproteins (LDLs), but other apheresis devices are more efficient at LDL removal ( Chapter 80 ).

Volume Exchanged

Typically, unless otherwise indicated, 1 to 1.5 plasma-volumes are exchanged approximately every other day based on the apheresis kinetics ( Figure 75.1 ). In addition to removing pathogenic substances, TPE also removes normal plasma constituents, such as coagulation factors, immunoglobulins, and platelets ( Table 75.1 ). In patients with normal bone marrow and liver function, endogenous synthesis replete most coagulation factors and platelets within 2–4 days. It is not advisable to check routine labs, such as coagulation (PT/aPTT and fibrinogen) and chemistry panels immediately post-TPE; it takes ∼24 hours for equilibrium to be established between intra- and extravascular spaces. Furthermore, different replacement fluids have different advantages and disadvantages ( Table 75.2 ). Regarding the type of replacement fluid used in TPE procedures, albumin and/or normal saline are usually given (the ratio of albumin to saline varies among institutions, but albumin is the predominant fluid given to prevent hypovolemic reactions) if plasma is not indicated. Plasma products are typically used only in the treatment of thrombotic microangiopathies (TMAs) and in patients with underlying coagulopathy, such as liver disease, and/or who are actively bleeding. In addition, plasma can be given at the end of the procedure to prevent coagulopathy in patients who need an invasive procedure immediately after TPE or to treat procedure-related coagulopathy.

Figure 75.1, Apheresis kinetics for IgG.

Table 75.1

Plasma Exchange Removal Following 1 Plasma Volume Therapeutic Plasma Exchange

From Weinstein, R., in McLeod, B. C., Weinstein, R., Winters, J. L., et al. (Eds.). (2010). Apheresis Principles and Practice (3rd ed.). Baltimore: AABB Press.

	% Removal	% Recovery at 48 Hours
Coagulation factors	25–50	80–100
Fibrinogen	63	65
Immunoglobulins	63	45
Paraproteins	20–30	Variable
Liver enzymes	55–60	100
Bilirubin	45	100
C3	63	60–100
Platelets	25–30	75–100

Table 75.2

Comparison of Replacement Fluid

From Chhibber, V. and King, K. E., in McLeod, B. C., Weinstein, R., Winters, J. L., et al. (Eds.). (2010). Apheresis Principles and Practice (3rd ed.). Baltimore: AABB Press.

Replacement Fluid	Advantage	Disadvantage
Crystalloid	Low cost Hypoallergenic No infectious risk	Hypooncotic No immunoglobulins No coagulation factors
Albumin	Iso-oncotic Minimal infectious risk	Higher cost No immunoglobulins No coagulation factors
Plasma	Immunoglobulins Coagulation factors Iso-oncotic	Infection risk Citrate toxicity Allergic reactions ABO compatibility

Drug Removal During Apheresis

TPE has been used to treat acute drug toxicity when other modalities such as gastric lavage, dialysis, hemoperfusion, and forced diuresis are ineffective. Drugs that are highly protein-bound and have small volumes of distribution are most effectively removed by TPE. More commonly, therapeutic drug clearance by TPE is a concern. A drug is most likely to be removed during distribution phase, and therefore, it is prudent to dose drugs after TPE and not immediately before. Data suggest that prednisone, digoxin, cyclosporine, ceftriaxone, valproic acid, and phenobarbital might not be removed by TPE. Salicylates and tobramycin should be supplemented after TPE, and phenytoin should be monitored.

Category I Indications

American Society for Apheresis recently published guidelines on TPE indications ( Table 74.3 ).

Acute Inflammatory Demyelinating Polyradiculoneuropathy (Guillain–Barre Syndrome)

TPE and intravenous immunoglobulin (IVIG) have demonstrated equal clinical efficacy in the treatment of this disease. Volume of exchange in TPE = (200–250 mL of plasma) × (body weight measured in kilograms), spread over 10–14 days.

ANCA-Associated Rapidly Progressive Glomerulonephritis (Granulomatosis With Polyangiitis; and Microscopic Polyangiitis) (Category I for Dialysis Dependent and Diffuse Alveolar Hemorrhage)

ANCA (antineutrophil cytoplasmic antibody) small vessel vasculitis is treated with corticosteroids and immunosuppressive drugs. TPE should be added in cases of severe renal disease or pulmonary hemorrhage. Daily TPE with plasma replacement fluid should be performed for diffuse alveolar hemorrhage (DAH); otherwise, every other day with albumin is recommended.

Antiglomerular Basement Membrane Disease (Goodpasture Syndrome)

This syndrome stems from antiglomerular basement membrane antibodies, which result in damage to alveolar and renal basement membranes. Patients are treated with cyclophosphamide, steroids, and TPE. TPE is performed daily or every other day with albumin as replacement fluid (unless DAH is present, in which case plasma is recommended).

Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy exhibits proximal and distal symmetric muscle weakness with or without numbness that becomes more severe for ≥2 months. Corticosteroids, TPE, and IVIG have similar efficacy. TPE is performed 2–3 times per week until the patient improves, and then frequency is tapered.

Focal Segmental Glomerulosclerosis

TPE is used in the management of patients with recurrent focal segmental glomerulosclerosis in a renal allograft. TPE is performed daily or every other day, and multiple regimens have been reported. Tapering the frequency of TPE is individually done based on patient’s proteinuria severity. Some patients require long-term exchanges as maintenance therapy.

Hyperviscosity in Monoclonal Gammopathies

Hyperviscosity, which may occur in disorders such as Waldenström macroglobulinemia and multiple myeloma, may result in a multitude of symptoms. Each patient has an individual viscosity for which he/she becomes symptomatic, most commonly around 6–7 cP. TPE removes paraproteins, thereby decreasing viscosity. TPE is initiated as soon as possible after diagnosis, followed by disease-specific treatments to prevent future accumulation of paraproteins. Daily 1–1.5 TPV with albumin as replacement fluid, typically 1–3 total. Patient status, serum viscosity, and paraprotein may all be considered when determining duration of TPE treatment.

Liver Transplantation

TPE may be used to reduce isoagglutinin titers in ABO-incompatible liver transplants. The replacement fluid for TPE is plasma (compatible with both donor and recipient), or a mixture of plasma and albumin. For desensitization, TPE will continue until a goal titer is achieved, but for rejection, the treatment is based on liver function. Individual institutions will determine their titer goals. Typically, 1–1.5 TPV is processed daily or every other day.

Myasthenia Gravis

Cholinesterase inhibitors, thymectomy, immunosuppression, and TPE or IVIG are the mainstays of myasthenia gravis therapy. Patients typically improve quickly with TPE but may need maintenance therapy. Albumin is used as replacement fluid, and the procedure is performed daily or every other day.

N-Methyl d -Aspartate Receptor Antibody Encephalitis

N-methyl d -aspartate receptor (NMDAR) encephalitis results from antibodies directed against the NMDAR GluN1 subunit. It results in a severe neurologic disease with many pronounced symptoms. Most patients are female, about half of whom have a neoplasm (this is most commonly an ovarian teratoma). When NMDAR encephalitis is diagnosed, a tumor should be ruled out and removed if discovered. Immunosuppression medications, IVIG, and TPE are primary treatment options. TPE should be performed with albumin every other day for 5–6 treatments.

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