Volume 52, Issue 6 , Pages 1180-1196, December 2008
Therapeutic Plasma Exchange: Core Curriculum 2008
Article Outline
- Introduction and Rationale
- Introduction and Rationale: Suggested Readings
- Indications
- Plasmapheresis and Renal Disease: Suggested Readings
- Reviews
- Anti-GBM Antibody–Mediated Disease
- Rapidly Progressive Glomerulonephritis
- Multiple Myeloma
- IgA Nephropathy and Henoch-Schönlein Purpura
- Cryoglobulinemia
- Thrombotic Thrombocytopenic Purpura
- HUS in the Adult
- HUS in Children
- Systemic Lupus Erythematosus
- Antiphospholipid Antibody Syndrome
- Scleroderma
- Focal Segmental Glomerulosclerosis
- Cytotoxic Antibody Removal
- Renal Allograft Rejection
- Renal Transplantation Across ABO Groups
- General Guidelines for Prescribing TPE
- General Guidelines for TPE Prescription: Suggested Reading
- Technique
- Technique: Suggested Readings
- Centrifugation
- Membrane Plasma Separation
- TPE With Dialysis Equipment
- Citrate Anticoagulation
- Replacement Fluids: Albumin
- Replacement Fluids: FFP
- Replacement Fluids: Starch
- Vascular Access
- Cascade Filtration Double Filtration
- Selective Plasmapheresis Techniques
- Cryofiltration
- Protein A Columns
- Prosorba Column
- Excorim
- Selective Lipid Removal
- Endotoxin Adsorption
- Complications
- Complications: Suggested Readings
- References for Table 1
- References for Table 3
- Copyright
Given their expertise in vascular access, anticoagulation, volume management, and solute clearance, nephrologists are well suited to manage all methods of blood purification, including therapeutic plasma exchange (TPE). This core curriculum is an annotated primer and bibliography for understanding the indications, technique, and complications associated with TPE.
Introduction and Rationale
TPE is an extracorporeal blood purification technique designed for the removal of large-molecular-weight substances. Examples of these substances include pathogenic autoantibodies, immune complexes, cryoglobulins, myeloma light chains, endotoxin, and cholesterol-containing lipoproteins.
For TPE to be a rational choice as a blood purification technique, at least 1 of the following conditions should be met: (1) the substance to be removed is sufficiently large (≥15,000 d) to make other less expensive purification techniques unacceptably inefficient (ie, hemofiltration or high-flux dialysis), (2) the substance to be removed has a comparatively prolonged half-life so that extracorporeal removal provides a therapeutically useful period of diminished serum concentration, and (3) the substance to be removed is acutely toxic and resistant to conventional therapy so that the rapidity of extracorporeal removal is clinically indicated.
The removal of pathogenic autoantibodies offers an example. If one considers that the natural half-life of immunoglobulin G (IgG) is approximately 21 days and assuming that an immunosuppressive agent could immediately halt production (unlikely), serum levels would still be 50% of the initial values for at least 21 days after initiating therapy. Such a delay might be unacceptable in the presence of a very aggressive autoantibody, such as that involved with Goodpasture syndrome.
Introduction and Rationale: Suggested Readings
Cohen S, Freeman T: Metabolic heterogeneity of human gamma globulin. Biochem J 76:475-487, 1960
Indications
In 1985, the American Medical Association (AMA) Council on Scientific Affairs convened a panel of 10 experts to review the available data for the efficacy of plasma exchange. Their assessment assigned each potential indication into 1 of 4 categories:
Since this AMA review, there have been several well-designed randomized controlled trials that added significant new insight into the proper application of TPE. In consideration of these new studies, 2 subsequent reviews have attempted to update the original AMA recommendations. Added to these updated reviews is an assessment by the American Academy of Neurology. Most recently, in June 2007, the American Society for Apheresis published their exhaustive review of the indications for plasma exchange and the most current assessment of the available supportive evidence. The rating system of this most-up-to-date review uses categories (I to IV) similar to the previous reviews.
The original AMA indications, updated and modified by the 4 subsequent reviews, are listed in Table 1.
Table 1. Indications for TPE
| Reference | 1 | 2 | 3 | 4 | 5 |
|---|---|---|---|---|---|
| Year | 1986 | 1993 | 1994 | 1996 | 2007 |
| Rating | Rating | Rating | Rating | Rating | |
| Neurological diseases | |||||
| I | I | I | est | I | |
| I | I | I | est | I | |
| III | I | I | est | I | |
| nl | II | nl | est | I-III | |
| II | III | III | pos | II-III | |
| nl | I | nl | pos | II | |
| nl | nl | nl | invest | III | |
| IV | IV | IV | nl | nl | |
| nl | nl | nl | invest | nl | |
| nl | nl | nl | invest | III | |
| nl | I | nl | invest | II | |
| nl | nl | nl | nl | nl | |
| Hematologic disorders | |||||
| I | I | I | I | ||
| II | I | I | I | ||
| I | I | I | I | ||
| nl | II | II | III-IV | ||
| III | III | III | II-IV | ||
| II | I | I | III | ||
| III | III | III | III | ||
| II | III | nl | II | ||
| II | II | III | III | ||
| Metabolic disorders | |||||
| II | I-II | I | I-II | ||
| nl | nl | nl | III | ||
| II | nl | nl | nl | ||
| III | III | nl | III | ||
| I | III | III | III | ||
| nl | nl | nl | nl | ||
| Dermatological disorders | |||||
| III | II | nl | III | ||
| nl | II | nl | nl | ||
| nl | nl | nl | nl | ||
| nl | nl | nl | nl | ||
| III | IV | IV | nl | ||
| Rheumatological disorders | |||||
| II | II | nl | III-IV | ||
| nl | nl | nl | III | ||
| III | III | III | III | ||
| II | III | IV&II | II | ||
| II | II | II | nl | ||
| III | III/IV | IV | nl | ||
| Renal disease | |||||
| I | I | I | I | ||
| I | II | II | III | ||
| II | II | nl | III | ||
| II | nl | nl | nl | ||
| nl | nl | nl | III | ||
| II | IV | IV | II | ||
| nl | nl | nl | II | ||
| Indications for TPE in the ICU | |||||
| nl | nl | nl | nl | ||
| nl | nl | nl | III | ||
| III | nl | nl | nl | ||
| III | nl | nl | nl | ||
| nl | II | nl | nl | ||
| nl | I | nl | nl | ||
| nl | I | nl | nl | ||
| Intoxications | I | II | II | II-III | |
| II | II | ||||
| II | |||||
| II | |||||
| II | |||||
Another means of assessing the standard of care currently acceptable in the United States is to refer to the current indications for which Medicare is willing to reimburse. This list of indications is available on the Medicare website and is reproduced in Table 2.
Table 2. Medicare Reimburseable Indications for Plasma Exchange⁎
| Apheresis is covered for the following indications: |
⁎Centers for Medicare and Medicaid Services: NCD for Apheresis (therapeutic Pheresis). Available at: http://www.cms.hhs.gov/mcd/viewncd.asp?ncd_id=110.14&ncd_version=1&basket=ncd%3A110%2E14%3A1%3AApheresis+%28Therapeutic+Pheresis%29. Accessed May 21, 2008. |
Therapeutic Apheresis for Renal Disorders
Many primary renal diseases are associated with autoantibodies, rendering them appealing indications for TPE. Some indications are well established by randomized controlled studies and are considered standard of care (Goodpasture and thrombotic thrombocytopenic purpura [TTP]). Others have less compelling or only anecdotal supporting evidence. Note: Subset analysis. All studies used concomitant treatment with steroids and immunosuppressive agents. To convert serum creatinine mg/dL to μmol/L, multiply by 88.4. Abbreviation: TPE, therapeutic plasma exchange. Table 3 adapted with permission from: Kaplan AA: A Practical Guide to Therapeutic Plasma Exchange. Blackwell Science, Malden, MA, 1999, copyright Andre Kaplan. ⁎P < 0.05 with day 0. †P < 0.05, TPE versus no TPE.Table 3. Controlled Trials of TPE for Patients With Severe or Dialysis-Dependent Rapidly Progressive Glomerulonephritis
Reference Index of severity TPE no TPE Mauri et al,1 1985 Creatinine > 9 mg/dL
Initial creatinine, mg/dL (no. of patients) 13.5
(6)13.1
(5)
Creatinine after 3 y (mg/dL) 8.7⁎ 13.4 Glockner et al,2 1988 Dialysis dependent
Initial creatinine, mg/dL (no. of patients) 7.4
(8)9.2
(4)
Creatinine after 6 mo 1.7⁎ 5.5 Pusey et al,3 1991 Dialysis dependent
Initial no. of patients on dialysis 11 8
Patients off dialysis at 12 mo 10† 3 Cole et al,4 1992 Dialysis dependent
Initial no. of patients on dialysis 4 7
Patients off dialysis at 12 mo 3 2 Jayne et al,5 2007 Creatinine > 5.8 mg/dL
Initial no. of patients 70 67
Patients off dialysis at 12 mo 57 40
Patients with Wegener granulomatosis and microscopic polyarteritis who present with pulmonary hemorrhage appear to be more likely to present with IgM antineutrophil cytoplasmic antibodies (ANCAs). These patients may also respond to TPE.
Although treatment success depends on the cause, HUS in adults is often treated with TPE as with TTP.
Plasmapheresis and Renal Disease: Suggested Readings
Reviews
Madore F, Lazarus JM, Brady HR: Therapeutic plasma exchange in renal disease. J Am Soc Nephrol 7:367-386, 1996
Kaplan AA: Therapeutic apheresis for renal disorders. Ther Apher 3:25-30, 1999
Anti-GBM Antibody–Mediated Disease
Johnson JP, Moore JJ, Austin H III, Balow JE, Antonovych TT, Wilson CB: Therapy of anti-glomerular basement membrane disease: Analysis of prognostic significance of clinical, pathologic and treatment factors. Medicine 64:219-227, 1985
Savage CO, Pusey CD, Bowman C, Rees AJ, Lockwood CM: Antiglomerular basement membrane antibody-mediated disease in the British isles 1980-4. Br Med J 292:301-304, 1986
Rapidly Progressive Glomerulonephritis
Esnault VL, Soleimani B, Keogan MT, Brownlee AA, Jayne DR, Lockwood CM: Association of IgM with IgG ANCA in patients presenting with pulmonary hemorrhage. Kidney Int 41:1304-1310, 1992
Kaplan AA: Therapeutic plasma exchange for the treatment of rapidly progressive glomerulonephritis (RPGN). Ther Apher I:255-259, 1997
Jayne DR, Gaskin G, Rasmussen N, et al, for the European Vasculitis Study Group: Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 18:2180-2188, 2007
Lionaki S, Falk RJ: Removing antibody and preserving glomeruli in ANCA small-vessel vasculitis. J Am Soc Nephrol 18:1987-1989, 2007
Multiple Myeloma
Zucchelli P, Pasquali S, Cagnoli L, Ferrari G: Controlled plasma exchange trial in acute renal failure due to multiple myeloma. Kidney Int 33:1175-1189, 1988
Clark WF, Stewart AK, Rock GA, et al: Plasma exchange when myeloma presents as acute renal failure: A randomized, controlled trial. Ann Intern Med 143:777-784, 2005
Rajkumar SV, Kaplan AA, Leung N: Treatment of renal failue in multiple myeloma, in Rose BD (ed): UpToDate. Waltham, MA, UpToDate, 2007
Hutchison CA, Cockwell P, Reid S, et al: Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: In vitro and in vivo studies. J Am Soc Nephrol 18:886-895, 2007
IgA Nephropathy and Henoch-Schönlein Purpura
Coppo R, Basolo B, Giachino O, et al: Plasmapheresis in a patient with rapidly progressive idiopathic IgA nephropathy: Removal of IgA-containing circulating immune complexes and clinical recovery. Nephron 40:488-490, 1985
Nicholls K, Becker G, Walker R, Wright C, Kincaid-Smith P: Plasma exchange in progressive IgA nephropathy. J Clin Apher 5:128-132, 1990
Cryoglobulinemia
Evans TW, Nicholls AJ, Shortland JR, Ward AM, Brown CB: Acute renal failure in essential mixed cryoglobulinemia: Precipitation and reversal by plasma exchange. Clin Nephrol 21:287-293, 1984
Ferri C, Moriconi L, Gremignai G, et al: Treatment of the renal involvement in mixed cryoglobulinemia with prolonged plasma exchange. Nephron 43:246-253, 1986
Thrombotic Thrombocytopenic Purpura
Rock GA, Shumak KH, Buskard NA, et al: Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. N Engl J Med 325:393-397, 1991
Raife TJ, Friedman KD, Dwyre DM: The pathogenicity of vWF factor in TTP: Reconsideration of treatment with cryopoor plasma. Transfusion 46:74-79, 2006
HUS in the Adult
Melnyk AMS, Solez K, Kjellstrand CM: Adult hemolytic uremic syndrome: A review of 37 cases. Arch Intern Med 155:2077-2084, 1995
Agarwal A, Mauer SM, Matas AJ, Nath KA: Recurrent hemolytic uremic syndrome in an adult renal allograft recipient: Current concepts and management. J Am Soc Nephrol 6:1160-1169, 1995
Kaplan AA: Therapeutic apheresis for cancer related hemolytic uremic syndrome. Ther Apher 4:201-206, 2000
HUS in Children
Gianviti A, Perna A, Caringella A, et al: Plasma exchange in children with hemolytic-uremic syndrome at risk of poor outcome. Am J Kidney Dis 22:264-266, 1993
Sheth KJ, Leichter HE, Gill JC, Baumgardt A: Reversal of central nervous system involvement in hemolytic uremic syndrome by use of plasma exchange. Clin Pediatr 26:651-656, 1987
Systemic Lupus Erythematosus
Lewis EJ, Hunsicker LG, Lan SP, Rohde RD, Lachin JM, for the Lupus Nephritis Collaborative Study Group: A controlled trial of plasmapheresis therapy in severe lupus nephritis. N Engl J Med 326:1373-1379, 1992
Antiphospholipid Antibody Syndrome
Asherson RA, Piette JC: The catastrophic antiphospholipid syndrome 1996: Acute multi-organ failure associated with antiphospholipid antibodies: A review of 31 patients. Lupus 5:414-417, 1996
Zar T, Kaplan AA: Predictable removal of anticardiolipin antibody by therapeutic plasma exchange in a patient with catastrophic antiphospholip antibody syndrome (CAPS). Clin Nephrol (in press)
Scleroderma
Endo H, Hosono T, Kondo H: Antineutrophil cytoplasmic autoantibodies in 6 patients with renal failure and systemic sclerosis. J Rheumatol 21:864-870, 1994
Wach F, Ullrich H, Schmitz G, Landthaler M, Hein R: Treatment of severe localized scleroderma by plasmapheresis—Report of three cases. Br J Dermatol 133:605-609, 1995
Focal Segmental Glomerulosclerosis
Dantal J, Bigot E, Bogers W, et al: Effect of plasma protein adsorption on protein excretion in kidney-transplant recipients with recurrent nephrotic syndrome. N Engl J Med 330:7-14, 1994
Matalon A, Markowitz GS, Joseph RE, et al: Plasmapheresis treatment of recurrent FSGS in adult renal transplant recipients. Clin Nephrol 56:271-278, 2001
Cytotoxic Antibody Removal
Ross CN, Gaskin G, Gregor-Macgregor S, et al: Renal transplantation following immunoadsorption in highly sensitized recipients. Transplantation 55:785-789, 1993
Renal Allograft Rejection
Kirubakaran MG, Disney APS, Norman J, Pugsley DJ, Mathew TH: A controlled trial of plasmapheresis in the treatment of renal allograft rejection. Transplantation 32:164-165, 1981
Bonomini V, Vangelista A, Frasca GM, Di Felice A, Liviano D'Arcangelo G: Effects of plasmapheresis in renal transplant rejection: A controlled study. Trans Am Soc Artif Intern Organs 31:698-701, 1985
Renal Transplantation Across ABO Groups
Tanabe K, Takahashi K, Agishi T, et al: Removal of anti-A/B antibodies for successful kidney transplantation between ABO blood type incompatible couples. Transfus Sci 17:455-462, 1996
Karakayali H, Moray G, Demira A, et al: Long-term follow-up of ABO-incompatible renal transplant recipients. Transplant Proc 31:256-257, 1999
Takahashi K, Saito K, Takahara S, et al: Excellent long-term outcome of ABO-incompatible living donor kidney transplantation in Japan. Am J Transplant 4:1089-1096, 2004
General Guidelines for Prescribing TPE
The amount of plasma to be exchanged during TPE must be determined in relation to the patient's estimated plasma volume (EPV). A simple means of estimating plasma volume can be calculated from the patient's weight and hematocrit using the following formula:
(1)
(2)
Figure 1.
Relation of volume exchanged, estimated plasma volume (EPV), and percentage of decrease in initial concentration for large-molecular-weight substances removed during therapeutic plasma exchange (TPE). For example, if the volume exchanged (Ve) is equal to the patient's EPV, Ve/EPV will equal 1 and pretreatment values will be decreased by 63%. If the plasma exchanged is equal to 1.4 times the EPV, pretreatment levels will be decreased by 75%. As shown in the figure, increasingly voluminous exchanges during a single treatment yield a progressively smaller decrease in pretreatment levels. For most indications, each treatment should provide an exchange volume equal to 1 to 1.4 times the EPV. (Reproduced from Kaplan AA: A Practical Guide to Therapeutic Plasma Exchange, copyright Andre Kaplan)
Extravascular to intravascular reequilibration of a large-molecular-weight substance will be relatively slow (∼1% to 3% per hour). Thus, several consecutive treatments separated by 24 to 48 hours each will have to be performed to remove a substantial percentage of the total-body burden. An example of the progressive reduction in serum levels of an immunoglobulin is shown in Fig 2, with a net 70% decrease in total-body IgG level 1 day after 3 consecutive TPE treatments equaling 1 plasma volume each. In general, if production rates (resynthesis) are modest (ie, slowly forming antibody), at least 5 separate treatments during a 7- to 10-day period will be required to remove 90% of the patient's initial total-body burden. If production rates are high (ie, rapidly forming antibody, complement components), additional treatments may be required.

Figure 2.
Progressive decrease in immunoglobulin G (IgG) levels after 3 consecutive therapeutic plasma exchange (TPE) treatments equaling 1 plasma volume each. Intertreatment increases between treatments represent a combination of extravascular to intravascular reequilibration and a variable amount of new IgG synthesis. (Reproduced from Kaplan AA: A Practical Guide to Therapeutic Plasma Exchange, copyright Andre Kaplan)
The results shown in Fig 2 describe a best-case scenario concerning immunoglobulin removal. In some autoimmune diseases, the rate of autoantibody production may greatly exceed that of the total immunoglobulin class. Such has been documented for certain cases of Goodpasture syndrome in which anti-GBM activity will be predictably decreased by a given plasma exchange treatment, but for which the intertreatment increases in serum levels are too rapid to be compatible with a simple reequilibration of extravascular stores. Thus, a 70% absolute decrease in a pathogenic autoantibody requires at least 3 plasma exchange treatments and may require a far more intensive treatment schedule if production rates cannot be adequately controlled by the concomitant immunosuppressive medications.
Production rates (half-lives), molecular weights, and percentages of intravascular distribution of several serum proteins are listed in Table 4.
Table 4. Distribution and Metabolism of Plasma Proteins
| Protein | Concentration (mg/mL) | MW × 103 d | Intravascular (%) | Fractional Turnover Rate (%/d) | Half-life (d) |
|---|---|---|---|---|---|
| Normal physiology | |||||
| 12 | 150 | 45 | 7 | 22 | |
| 0.7 | 150 | 64 | 17 | 7 | |
| 0.9 | 950 | 78 | 19 | 5 | |
| 2.5 | 160 | 42 | 25 | 6 | |
| 0.02 | 175 | 75 | 37 | 2.8 | |
| 0.0001 | 190 | 45 | 94 | 2.5 | |
| 45 | 66 | 44 | 11 | 17 | |
| 1.4 | 240 | 67 | 41 | 2 | |
| 0.5 | 200 | 66 | 43 | 2 | |
| 3-4 | 340 | 81 | 24 | 4.2 | |
| 0.1 | 100-340 | 71 | 150 | 0.6 | |
| 0.2 | 56-58 | 45 | 55 | 2.4 | |
| 1.5-2.0 | 1,300 | >90 | 3-5 | ||
| Pathological conditions | |||||
| 50-130 | 950 | 89 | 25⁎ | 5.9 | |
| 4-10 | 10-25 | <50 | † | † | |
| 3-25 × 10-7 | 100-2,400⁎ | >50 | ‡ | ‡ | |
| ⁎ | >300⁎ | >50 | ‡ | ‡ | |
| Tumor necrosis factor | 3-5 × 10-7 | 50 (trimer) | <50 | 6-20 min |
⁎Highly variable or poorly defined. |
†Highly dependent on degree of renal function, half-life greatly increased with renal failure. |
‡Half life will be variable and dependent on the clearing capabilities of the reticuloendothelial system. |
General Guidelines for TPE Prescription: Suggested Reading
Kaplan AA: A simple and accurate method for prescribing plasma exchange. Trans Am Soc Artif Intern Organs 36:M597-M599, 1990
Kaplan AA: Towards a rational prescription of plasma exchange: The kinetics of immunoglobulin removal. Semin Dial 5:227-229, 1992
Technique
Traditionally, plasma exchange was performed with centrifugation devices used in blood-banking procedures. These devices offer the advantage of allowing for selective cell removal (cytapheresis). Plasma exchange also can be performed using a highly permeable filter and standard dialysis equipment.
Technique: Suggested Readings
Gurland HJ, Lysaght MJ, Samtleben W, Schmidt B: A comparison of centrifugal and membrane based apheresis formats. Int J Artif Organs 7:35-38, 1984
Centrifugation
Sowada K, Malchesky PS, Nose Y: Available removal systems: State of the art, in Nydegger UE (ed): Therapeutic Hemapheresis in the 1990s. Curr Stud Hematol Blood Transf 57:51-113, 1990
Membrane Plasma Separation
Gurland HJ, Lysaght MJ, Samtleben W, Schmidt B: Comparative evaluation of filters used in membrane plasmapheresis. Nephron 36:173-182, 1984
Sueoka A: Present status of apheresis technologies: Part 1. Membrane plasma separator. Ther Apher 1:42-48, 1997
TPE With Dialysis Equipment
Gerhardt RE, Ntoso KA, Koethe JD, Lodge S, Wolf CJ: Acute plasma separation with hemodialysis equipment. J Am Soc Nephrol 2:1455-1458, 1992
Price CA, McCarley PB: Technical considerations of therapeutic plasma exchange as a nephrology nursing procedure. ANNA J 20:41-46, 1993
Citrate Anticoagulation
Hester JP, McCullough J, Mishler JM, Szymanski IO: Dosage regimens for citrate anticoagulants. J Clin Apher 1:149-157, 1983
Replacement Fluids: Albumin
Finlayson JS: Albumin products. Semin Thromb Hemost 6:85-120, 1980
Replacement Fluids: FFP
AuBuchon JP, Birkmeyer JD, Busch MP: Safety of the blood supply in the United States: Opportunities and controversies. Ann Intern Med 127:904-909, 1997
Replacement Fluids: Starch
Brecher ME, Owen HG, Bandarenko N: Alternatives to albumin: Starch replacement for plasma exchange. J Clin Apher 12:146-153, 1997
Vascular Access
Mokrzycki MH, Zhang M, Golestaneh L, Laut J, Rosenberg SO: An interventional controlled trial comparing 2 management models for the treatment of tunneled cuffed catheter bacteremia: A collaborative team model versus usual physician-managed care. Am J Kidney Dis 48:587-595, 2006
Cascade Filtration Double Filtration
Agishi T, Kaneko I, Hasuo Y, et al: Double filtration plasmapheresis. Trans Am Soc Artif Intern Organs 26:406-409, 1980
Selective Plasmapheresis Techniques
Malchesky PS, Kaplan AA, Coo AP, Sadurada Y, Siami GA: Are selective macromolecule removal plasmapheresis systems useful for autoimmune diseases or hyperlipidemia? ASAIO J 39:868-872, 1993
Cryofiltration
Vibert GJ, Wirtz SA, Smith JW, et al: Cryofiltration as an alternative to plasma exchange: Plasma macromolecular solute removal without replacement fluids, in Nose Y, Malchesky PS, Smith JW (eds): Plasmapheresis. Cleveland, OH, ISAO, 1983, pp 281-287
Protein A Columns
Samtleben W, Schmidt B, Gurland HJ: Ex vivo and in vivo protein A perfusion: Background, basic investigations and first clinical experience. Blood Purif 5:179-192, 1987
Prosorba Column
Brecher ME, Owen Hg, Collins ML: Apheresis and ACE inhibitors. Transfusion 33:963-964, 1993 (letter)
Feldon DT, LeValley MP, Baldassare AR, et al. The Prosorba column for treatment of refractory rheumatoid arthritis. A randomized, double blind, sham controlled trial. Arthritis Rheum 42:2153-2159, 1999
Excorim
Hakim RM, Milford E, Himmelfarb J, Wingard R, Lazarus JM, Watt RM: Extracorporeal removal of anti-HLA antibodies in transplant candidates. Am J Kidney Dis 16:423-431, 1990
Ross CN, Gaskin G, Gregor-Macgregor S, et al: Renal transplantation following immunoadsorption in highly sensitized recipients. Transplantation 55:785-789, 1993
Selective Lipid Removal
Saal SD, Parker TS, Gordon BR: Removal of low-density lipoproteins in patients by extracorporeal immunoadsorption. Am J Med 80:583-589, 1986
Gordon BR, Kelsey SF, Bilheimer DW, et al: Treatment of refractory familial hypercholesterolemia by low density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. Am J Cardiol 70:1010-1016, 1992
Busnach G, Cappelleri A, Vaccarino V, et al: Selective and semiselective low-density lipoprotein apheresis in familial hypercholesterolemia. Blood Purif 6:156-161, 1988
Kroon AA, van Asten WNJC, Stalenhoef AFH: Effect of apheresis of low-density lipoprotein on peripheral vascular disease in hypercholesterolemic patients with coronary artery disease. Ann Intern Med 125:945-954, 1996
Jovin IS, Taborski U, Stehr A, Müller-Berghaus G: Lipid reductions by low-density lipoprotein apheresis: A comparison of three systems. Metabolism 49:1431-1433, 2000
Bosch T, Gahr S, Belschner U, Schaefer C, Lennertz A, Rammo J, for the DALI Study Group: Direct adsorption of low-density lipoprotein by DALI-LDL-apheresis: Results of a prospective long-term multicenter follow-up covering 12,291 sessions. Ther Apher Dial 10: 210-218, 2006
Endotoxin Adsorption
Aoki H, Kodama M, Tani T, Hanasawa K: Treatment of sepsis by extracorporeal elimination of endotoxin using polymyxin B-immobilized fiber. Am J Surg 167:412-417, 1994
Complications
Most common: citrate-induced parethesias, muscle cramps, urticaria (Table 5).
Table 5. Complications of Plasmapheresis
| Symptom | Percentage |
|---|---|
| Urticaria | 0.7-12 |
| Paresthesias | 1.5-9 |
| Muscle cramps | 0.4-2.5 |
| Dizziness | <2.5 |
| Headaches | 0.3-5 |
| Nausea | 0.1-1 |
| Hypotension | 0.4-4.2 |
| Chest pain | 0.03-1.3 |
| Arrhythmia | 0.1-0.7 |
| Anaphylactoid reactions | 0.03-0.7 |
| Rigors | 1.1-8.8 |
| Hyperthermia | 0.7-1.0 |
| Bronchospasm | 0.1-0.4 |
| Seizure | 0.03-0.4 |
| Respiratory arrest/pulmonary edema | 0.2-0.3 |
| Myocardial ischemia | 0.1 |
| Shock/myocardial infarction | 0.1-1.5 |
| Metabolic alkalosis | 0.03 |
| Disseminated intravascular coagulation | 0.03 |
| Central nervous system ischemia | 0.03-0.1 |
| Hepatitis | 0.7 |
| Hemorrhage | 0.2 |
| Hypoxemia | 0.1 |
| Pulmonary embolism | 0.1 |
| Access related | |
| 0.02-0.7 | |
| 0.3 | |
| 0.1 | |
| 0.08-4 |
Most serious: anaphylactoid reactions to FFP
Incidence of death is 0.05%, but many patients have severe preexisting conditions Abbreviations: IgA, immunoglobulin A; ACE, angiotensin-converting enzyme; ITP, idiopathic thrombocytopenic purpura; TPE, therapeutic plasma exchange. Reproduced from: Kaplan AA: A Practical Guide to Therapeutic Plasma Exchange. Blackwell Science, Malden, MA, 1999, copyright Andre Kaplan. Note: In general, drugs with a high percentage of protein binding and a modest volume of distribution are likely to be removed by plasma exchange. Reproduced from: Kaplan AA: A Practical Guide to Therapeutic Plasma Exchange. Blackwell Science, Malden, MA, 1999, copyright Andre Kaplan.Table 6. Potential Causes for Hypotension During TPE
Delayed or inadequate volume replacement Vasovagal episodes Hypo-oncotic fluid replacement: 3.5% albumin solutions Anaphylaxis:
Reactions to plasma components in replacement fluids
Anti-IgA antibodies (IgA-deficient patient)
Endotoxin-contaminated replacement fluid
Reactions to bioincompatible membranes
Sensitivity to ethylene oxide
Device-related: Prosorba protein A columnCardiac arrhythmia
Citrate-induced hypocalcemia
Hypokalemic related (especially in patients on digitalis therapy)Bradykinnin reactions (cf reactions to ACE inhibitors) Hemorrhage
Associated with primary disease (ITP, factor VIII inhibitors)
Associated with heparin anticoagulation
Associated with vascular access
External
Internal
“Depletion” coagulopathyCardiovascular collapse Pulmonary embolus Disease-related hypotension
Guillain-Barre syndrome (autonomic dysfunction)
Waldenstrom macroglobulinemia (rapid decrease in plasma volume)Table 7. Drugs With a High Percentage of Protein Binding and Modest Volume of Distribution
Protein Binding (%) Volume of Distribution (L/kg) Acetylsalicylic acid 50-90 0.1-0.2 Cefazolin 80 0.13-0.22 Cefotetan 85 0.15 Ceftriaxone 90 0.12-0.18 Chlorpropamide 72-96 0.09-0.27 Diclofenac >99 0.12-0.17 Dicloxacillin 95 0.16 Glyburide 99 0.16-0.3 Heparin >90 0.06-0.1 Ibuprofen 99 0.15-0.17 Indomethacin 99 0.12 Ketorolac >99 0.13-0.25 Naproxen 99 0.10 Probenecid 85-95 0.15 Sodium valproate 90 0.19-0.23 Streptokinase ? 0.02-0.08 Tolbutamide 95-97 0.10-0.15 Warfarin 97-99 0.11-0.15
Complications: Suggested Readings
Sutton DMC, Nair RC, Rock G, and the Canadian Apheresis Study Group: Complications of plasma exchange. Transfusion 29:124-127, 1989
Mokrzycki MF, Kaplan AA: Therapeutic plasma exchange: Complications and management. Am J Kidney Dis 23:817-827, 1994
Citrate-Induced Hypocalcemia
Silberstein LE, Naryshkin S, Haddad JJ, Strauss JF: Calcium homeostasis during therapeutic plasma exchange. Transfusion 26:151-155, 1986
Coagulation Abnormalities
Wood L, Jacobs P: The effect of serial therapeutic plasmapheresis on platelet count, coagulation factors plasma immunoglobulin and complement levels. J Clin Apher 3:124-128, 1986
Sultan Y, Bussel A, Maisonneuve P, Sitty X, Gajdos P: Potential danger of thrombosis after plasma exchange in the treatment of patients with immune disease. Transfusion 19:588-593, 1979
Infection
Pohl MA, Lan SP, Berl T, and the Lupus Nephritis Collaborative Study Group: Plasmapheresis does not increase the risk for infection in immunosuppressed patients with severe lupus nephritis. Ann Intern Med 114:924-929, 1991
Schreiber GB, Busch MP, Kleinman SH, Korelitz JJ: The risk of transfusion-transmitted virus invections. The Retrovirus Epidemiology Donor Study. N Engl J Med 334:1685-1690, 1996
Reactions to Protein-Containing Solutions
Apter AJ, Kaplan AA: An approach to immunologic reactions with plasma exchange. J Allergy Clin Immunol 90:119-124, 1992
Atypical Reactions to ACE Inhibitors
Owen HG, Brecher ME: Atypical reactions associated with use of angiotensin-converting enzyme inhibitors and apheresis. Transfusion 34:891-894, 1994
Olbricht CJ, Schauman D, Fisher D: Anaphylactoid reactions, LDL apheresis with dextran sulfate and ACE inhibitors. Lancet 3:340:908-909, 1992
Electrolyte Abnormalities
Pearl RG, Rosenthal MH: Metabolic alkalosis due to plasmapheresis. Am J Med 79:391-393, 1985
Milliner DS, Shinaberger JH, Shurman P, Coburn JW: Inadvertent aluminum administration during plasma exchange due to aluminum contamination of albumin replacement solutions. N Engl J Med 312:165-167, 1985
Vitamin Removal
Reddi A, Frank O, DeAngelis B, et al: Vitamin status in patients undergoing single or multiple plasmapheresis. J Am Coll Nutr 6:485-489, 1987
Miscellaneous Complications
MacDonald R, Robinson A: Suxamethonium apnea associated with plasmapheresis. Anaesthesia 35:198-201, 1980
Jorstad S: Biocompatibility of different hemodialysis and plasmapheresis membranes. Blood Purif 5:123-137, 1987
Nicholls AJ, Platts MM: Anaphylactoid reactions due to haemodialysis, haemofiltration or membrane plasma separation. Br Med J 285:1607-1609, 1982
Deaths
Huestis DW: Mortality in therapeutic haemapheresis. Lancet 1:1043, 1983 (letter)
Drug Removal
Jones JV: The effect of plasmapheresis on therapeutic drugs. Dial Transplant 14:225-226, 1985
References for Table 1
- . Current status of therapeutic plasmapheresis. JAMA. 1985;253:819–825
- An overview of current management. J Clin Apher. 1993;8:189–194
- . Guidelines for Therapeutic Hemapheresis. Bathesda, MD: American Association of Blood Banks; 1994;
- . Assessment of plasmapheresis (Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology). Neurology. 1996;47:840–843
- Guidelines on the use of therapeutic apheresis in clinical practice: evidence-based approach from the Apheresis Applications Committee of the American Society for Apheresis. J Clin Apher. 2007;22:106–175
References for Table 3
- Therapeutic plasma exchange in the treatment of rapidly progressive glomerulonephritis. Plasma Ther Transfus Technol. 1985;6:587–591
- Plasma exchange and immunosuppression in rapidly progressive glomerulonephritis: A controlled multi-center study. Clin Nephrol. 1988;29:1–8
- . Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies. Kidney Int. 1991;40:757–763
- A prospective randomized trial of plasma exchange as additive therapy in idiopathic crescentic glomerulonephritis. Am J Kidney Dis. 1992;20:261–269
- Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007;18:2180–2188
Originally published online as doi:10.1053/j.ajkd.2008.02.360 on June 17, 2008.
PII: S0272-6386(08)00707-5
doi:10.1053/j.ajkd.2008.02.360
© 2008 National Kidney Foundation, Inc. Published by Elsevier Inc All rights reserved.
Volume 52, Issue 6 , Pages 1180-1196, December 2008
