Therapeutic Plasma Exchange

Brittany Heady

Tingting Li

General Principles

Therapeutic plasma exchange (TPE) is an extracorporeal blood separation procedure in which a large volume of plasma is separated from the cellular components of blood, removed from the patient, and replaced with a colloid solution such as fresh frozen plasma (FFP) or albumin.¹
Rationale for TPE
- Removal of high-molecular weight, circulating pathogenic substances such as autoantibodies, alloantibodies, immune complexes, paraproteins, nonimmunoglobulin proteins (such as permeability factor in primary focal segmental glomerulosclerosis), and possibly proinflammatory cytokines and other inflammatory mediators.
- Replacement of deficient plasma factor, such as ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in thrombotic thrombocytopenic purpura (TTP).
- Modulation of immune system which has been shown to lead to improved macrophage/monocyte function and increased susceptibility of antibody-producing cells to cytotoxic therapies.

Current Renal Indications for TPE

TPE has been used in a variety of renal disorders, most often as an adjunct therapy, to rapidly remove existing pathogenic factors with the goals of ameliorating inflammation and achieving early disease control.²
However, the role of TPE in the management of certain renal disorders remains controversial, mainly due to lack of high-quality data.³ Table 23-1 lists the renal disorders for which TPE is recommended by the American Society for Apheresis as first-line therapy (category I indication), either as initial monotherapy or as adjunct therapy to immunosuppression.
Evidence supporting the use of TPE for specific renal disorders is presented in the treatment section of each disease entity discussed in this book.

Methods of Plasma Exchange

TPE can be performed using one of two technical methodologies: centrifugation or membrane plasma separation.⁴
In both approaches, whole blood is passed through a separation device in which plasma is removed and cellular components of blood are returned to the patient along with replacement solution.
Centrifugal separation is the more widely employed method in the United States.

TABLE 23-1 AMERICAN SOCIETY FOR APHERESIS 2016 CATEGORY I RENAL INDICATIONS AND TARGET MOLECULES FOR THERAPEUTIC PLASMA EXCHANGE

Renal Disease	Indication	Pathogenic Molecule
Anti-GBM disease	Diffuse alveolar hemorrhage Dialysis independence	Anti-GBM antibody
ANCA-associated vasculitis	Diffuse alveolar hemorrhage Dialysis dependence	ANCA
Focal segmental glomerulosclerosis	Recurrence in transplanted kidney	Permeability factor(s)
Thrombotic microangiopathy, complement mediated	Factor H autoantibody	Factor H autoantibody
Thrombotic thrombocytopenic purpura	Autoantibody to ADAMTS13 protease or deficiency of ADAMTS13	Autoantibody to ADAMTS13 protease
Renal transplantation, ABO compatible	Antibody mediated rejection Desensitization, living donor	Alloantibodies to HLA
Renal transplantation, ABO incompatible	Desensitization, living donor	Alloantibodies to HLA
GBM, glomerular basement membrane; ANCA, antineutrophil cytoplasmic antibody; ADAMTS13, a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13; HLA, human leukocyte antigen. Adapted from Schwartz J, Padmanabhan A, Aqui N, et al. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the writing committee of the American Society for Apheresis: The seventh special issue. J Clin Apher. 2016;31:149–162.

Centrifugation

This approach uses centrifugal force to separate blood components based on their density or specific gravity.
This is usually a continuous-flow method where blood from the patient is delivered into a spinning chamber (the centrifuge) and different components of blood are separated into layers based on their densities.
Plasma, being the least dense, forms the innermost layer. Of the cellular elements, red blood cells are the heaviest and settle on the outside of the chamber and platelets are the lightest and layers next to plasma, while white blood cells are in between. In TPE, plasma is collected from the chamber and discarded. The cells are returned to the patient with replacement fluid.
If desired, individual cellular component can also be collected with this method (cytapheresis).
Given the proximity of platelets to the plasma layer, loss of platelets can occur with removal of plasma with ensuing thrombocytopenia.

Membrane Plasma Separation

This method adopts the hemodialysis technology and is largely performed by dialysis nurses and supervised by nephrologists who are experts in extracorporeal blood purification.
Membrane plasma separation uses hollow-fiber filters to separate plasma from the cellular elements of whole blood by filtration based on the molecular weight of proteins.
The filters are highly permeable, with a molecular weight cut-off of up to 3 million Daltons, allowing the passage and removal of essentially all pathogenic molecules listed in Table 23-1, as well as larger molecules such as IgM and cryoglobulins. Blood cells are retained due to their significantly larger sizes.
This procedure is performed using the standard hemodialysis machines in the ultrafiltration mode. Both PrismaFlex and NxStage System One have been used at our center with success.
Membrane plasma separation uses higher blood flow rates compared to centrifugation to prevent filter clotting. This in turn leads to faster plasma removal and exchange rates and generally shorter duration of treatment (1 to 2 hours per TPE session).
Transmembrane pressure needs to be monitored closely and kept below 75 mm Hg to prevent hemolysis.