Clinical Policy Title: Plasmapheresis and plasma exchange

Transcription

1 Clinical Policy Title: Plasmapheresis and plasma exchange Clinical Policy Number: Effective Date: October 1, 2016 Initial Review Date: July 20, 2016 Most Recent Review Date: July 20, 2017 Next Review Date: July 2018 Policy contains: Plasmapheresis. Therapeutic plasma exchange. Related policies: CP# CP# Lipoprotein apheresis Intravenous Immunoglobulin ABOUT THIS POLICY: AmeriHealth Caritas of Louisiana has developed clinical policies to assist with making coverage determinations. AmeriHealth Caritas of Louisiana s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peer-reviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of medically necessary, and the specific facts of the particular situation are considered by AmeriHealth Caritas of Louisiana when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. AmeriHealth Caritas of Louisiana s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. AmeriHealth Caritas of Louisiana s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, AmeriHealth Caritas of Louisiana will update its clinical policies as necessary. AmeriHealth Caritas of Louisiana s clinical policies are not guarantees of payment. Coverage policy AmeriHealth Caritas of Louisiana considers the use of plasmapheresis/therapeutic plasma exchange (TPE) to be clinically proven and, therefore, medically necessary as a first-line treatment, either as a stand-alone treatment or in conjunction with other modes of treatment, for persons with the following conditions: ABO-compatible cardiac transplantation in combination with other immunomodulary therapies for desensitization or antibody-mediated rejection (AMR) (Category III exception). ABO-compatible renal transplantation for AMR or human leukocyte antigen (HLA) desensitization. ABO-incompatible renal transplantation for desensitization (live donor). ABO-incompatible liver transplantation for desensitization (live donor). Acute inflammatory demyelinating polyneuropathies (Guillain-Barré syndrome). Anti-glomerular basement membrane disease (Goodpasture s syndrome), either: - Diffuse alveolar hemorrhage (DAH). - Dialysis independent. 1

2 Antineutrophil cytoplasmic autoantibodies (ANCA)-associated rapidly progressive glomerulonephritis (granulomatosis with polyangiitis; microscopic polyangiitis), dialysisdependent. ANCA-associated rapidly progressive glomerulonephritis (granulomatosis with polyangiitis; microscopic polyangiitis), DAH. Chronic inflammatory demyelinating polyradiculoneuropathy. Hyperviscosity in monoclonal gammopathies, either: - Symptomatic. - As prophylaxis for rituximab treatment. Myasthenia gravis that is moderate to severe or as treatment pre-thymectomy. N-methyl D-aspartate receptor antibody encephalitis. Paraproteinemic demyelinating polyneuropathies types IgG, IgA, and IgM. Progressive multifocal leukoencephalopathy, associated with nataluziamab. Recurrent focal segmental glomerulosclerosis after kidney transplantation. Thrombotic microangiopathy, associated with Ticlopidine use. Thrombotic microangiopathy, complement-mediated-factor H autoantibodies. Thrombotic thrombocytopenic purpura. Wilson disease (fulminant). AmeriHealth Caritas of Louisiana considers the use of plasmapheresis/tpe to be clinically proven and, therefore, medically necessary as a second-line treatment, either as a stand-alone treatment or in conjunction with other modes of treatment, for the following conditions: ABO incompatible renal transplantation, humoral rejection. ABO-incompatible hematopoietic stem cell transplantation (HSCT), major hematopoietic progenitor cell (HPC), apheresis. ABO incompatible HSCT, major HPC, marrow. Acute disseminated encephalomyelitis. Acute fulminant central nervous system (CNS) demyelination, associated with multiple sclerosis or other conditions (e.g., transverse myelitis) refractory to corticosteroid therapy. Acute neuromyelitis optica spectrum disorders, acute. Autoimmunic hemolytic anemia, cold agglutinin disease type. Catastrophic antiphospholipid syndrome. Cryoglobulinemia that is symptomatic or severe. Familial hypercholesterolemia, homozygous type in persons with small blood volume. Hashimoto s encephalopathy, steroid-responsive encephalopathy associated with autoimmune thyroiditis. Lambert-Eaton myasthenic syndrome. Mushroom (wild) poisoning. Myeloma with acute renal failure. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal Infections (PANDAS), exacerbation. Phytanic acid storage disease (Refsum s disease). 2

3 Systemic lupus erythematosus (life-threatening). Vasculitis, hepatitis B virus polyarteritis nodasa (HBV-PAN). Voltage gated potassium channel antibodies (fulminant). Limitations: Plasmapheresis/TPE is contraindicated in the following members: Cannot tolerate central line placement. Active sepsis or hemodynamically unstable. Allergies to fresh frozen plasma (FFP) or albumin depending on the type of plasma exchange. With heparin allergies should not receive heparin as an anticoagulant during plasmapheresis. At risk for worsening hypocalcemia because citrate is commonly used to prevent clotting and can potentiate hypocalcemia. For the American Society for Apheresis (ASFA) conditions listed as Category III, TPE may be indicated as second- or third-line treatment or for unlisted conditions where removal of a pathogenic antibody makes biological sense providing there is no published evidence that TPE is ineffective or detrimental in the condition (See Appendix). All ASFA Category IV indications for plasmapheresis/tpe are not medically necessary (See Appendix). For Medicare members only: AmeriHealth Caritas of Louisiana considers the use of plasmapheresis/tpe to be clinically proven and, therefore, medically necessary for the following indications when performed either in a hospital setting (either inpatient or outpatient) or in a nonhospital setting where: a physician (or physicians) is present to perform medical services and to respond to medical emergencies at all times during patient care hours; each patient is under the care of a physician; and all nonphysician services are furnished under the direct, personal supervision of a physician: TPE for acquired myasthenia gravis. Plasmapheresis in the treatment of primary macroglobulinemia (Waldenstrom). Treatment of hyperglobulinemias, including (but not limited to) multiple myelomas, cryoglobulinemia, and hyperviscosity syndromes. Plasmapheresis or TPE as a last resort treatment of thromobotic thrombocytopenic purpura (TTP). Plasmapheresis or TPE in the last resort treatment of life-threatening rheumatoid vasculitis. TPE in the treatment of Goodpasture's syndrome. TPE in the treatment of glomerulonephritis associated with antiglomerular basement membrane antibodies and advancing renal failure or pulmonary hemorrhage. Treatment of chronic relapsing polyneuropathy for patients with severe or life-threatening symptoms who have failed to respond to conventional therapy. 3

4 Treatment of life-threatening scleroderma and polymyositis when the patient is unresponsive to conventional therapy. Treatment of Guillain-Barré syndrome. Treatment of last resort for life-threatening systemic lupus erythematosus when conventional therapy has failed to prevent clinical deterioration. Alternative covered services: Standard of care specific to each clinical condition. Background Apheresis is the extracorporeal, autologous process of removing one or more blood constituents from whole blood and returning the remainder to the circulation.therapeutic apheresis (also called blood component therapy) involves removal of the abnormal, pathogenic component, which, theoretically, should improve the disease course. Depending on clinical use, apheresis may be performed as a one-time-only treatment or several times per week for several weeks. For some, it may be a life-long commitment. Several apheresis techniques are available and differ in their underlying mechanisms of action (i.e., adsorption, precipitation, or selective filtration), depending on the blood component being removed. They are: Plasmapheresis using centrifugation or semipermeable membranes. Cytoreductive apheresis (e.g., erthythrocytopheresis, leukapheresis, and plateletpheresis) using centrifugation. Extracorporeal photopheresis involving leukapheresis centrifugation, photoactivation, and reinfusion of treated cell product back to the patient. Extracorporeal immunoadsorption with plasma reinfusion, also referred to as protein immunoadsorption therapy or by the trade name Prosorba Column (Cypress Bioscience, San Diego, California), using a highly purified protein complex bonded to a silica matrix. Extracorporeal selective adsorption or selective filtration of lipoproteins with plasma reinfusion (lipoprotein apheresis). Therapeutic plasmapheresis/therapeutic plasma exchange: The terms plasmapheresis and therapeutic plasma exchange are often used interchangeably, but there are technical distinctions between the two procedures. According to the ASFA, therapeutic plasmapheresis removes plasma (i.e., less than 15 percent of total plasma volume) from whole blood without the use of replacement solution, whereas TPE involves removal of plasma from whole blood and fluid replacement (Schwartz, 2013). Options for replacement fluid include albumin, electrolyte solutions, FFP and purified protein products such as individual clotting factors or antithrombin III. The choice of replacement product depends on the underlying condition and the risks and benefits associated with each replacement product. 4

5 Albumin is the most common replacement product because of its low side-effect profile and broad availability. Risks associated with the procedure include infection, hypotension, hypothermia, hypocalcemia, hypomagnesemia, and reactions to plasma replacement during and after the procedure. Patients can become thrombocytopenic and hypofibrinogenemic after plasmapheresis (especially if albumin is being used as a replacement product) and should be monitored for signs of bleeding. Delayed transfusion reactions can be seen several days after the transfusion ends (Schwartz, 2013; Howell, 2015). Searches AmeriHealth Caritas of Louisiana searched PubMed and the databases of: UK National Health Services Centre for Reviews and Dissemination. Agency for Healthcare Research and Quality s National Guideline Clearinghouse and other evidence-based practice centers. The Centers for Medicare & Medicaid Services (CMS). We conducted searches on June 26, Search terms were: Plasmapheresis(MeSH) and Plasma Exchange (MeSH). We included: Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies. Guidelines based on systematic reviews. Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies which also rank near the top of evidence hierarchies. Findings There is a large volume of literature on this topic, including multiple systematic reviews, meta-analyses and evidence-based guidelines for numerous clinical indications. We based this policy on evidence-based guidance from the Apheresis Applications Committee of the ASFA, which is responsible for reviewing, updating, and categorizing indications for therapeutic apheresis (Schwartz, 2013; Appendix). They use rigorous methodology to summarize the evidence for each indication and assign each indication to a category based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system for determining the quality of evidence and strength of recommendations (Schwartz, 2013; Guyatt, 2006): 5

6 I. Disorders for which apheresis is accepted as first-line therapy, as a primary stand-alone treatment. II. Disorders for which apheresis is accepted as second-line therapy, either as a stand-alone treatment or in conjunction with other modes of treatment. III. Optimum role of apheresis therapy is not established. Decision-making should be individualized. IV. Disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful. Institutional review board approval is desirable if apheresis treatment is undertaken in these circumstances. The British Committee for Standards in Haematology (BCSH) recommends following current ASFA guidelines for TPE (Howell, 2015). Similarly, the American Academy of Neurology (AAN) applied earlier ASFA guidelines and multiple Cochrane reviews to produce consensus recommendations for TPE in neurology (Cortese, 2013). TPE is indicated for conditions listed as ASFA Category I or Category II. TPE may be indicated as second- or third-line treatment for conditions listed as Category III or for unlisted conditions where removal of a pathogenic antibody makes biological sense, providing there is no published evidence that TPE is ineffective or detrimental in the condition. TPE should not be used for conditions where published evidence suggests harm or lack of benefit, such as Category IV conditions (Howell, 2015). Highly sensitized patients in need of cardiac transplantation face major challenges in obtaining a compatible allograft. Several transplantation programs around the United States have employed desensitization protocols to enlarge the pool of potential donors and using TPE in combination with other immunomodulary therapies (Colvin, 2015). The ASFA lists ABO-compatible cardiac transplantation as a Category III condition for which TPE has a role in acute desensitization and AMR (Schwartz, 2013). Both the American Heart Association and the International Society of Heart and Lung Transplantation recommend TPE as one of several immunomodulary options for desensitization or treatment of AMR in cardiac transplantation (Colvin, 2015; Costanzo, 2010). It is reasonable to include TPE in cardiac transplantation as a medically necessary indication. TPE protocols vary among conditions and local apheresis units (Howell, 2015). Many centers initially perform a run of five exchanges at 100 percent plasma volume daily or alternate-day intervals for the majority of indications, avoiding weekend days unless there is clinical urgency. For certain conditions (e.g., TTP, Goodpasture s disease, prophylaxis and treatment of solid organ transplant rejection due to anti-abo or anti-hla antibodies, and ANCA-associated vasculitides), more intensive exchange regimens are necessary often based on ASFA guidelines and other published evidence. Maintenance TPE is reserved for rare conditions such as hyperviscosity, cryoproteinemia, and antibody-mediated conditions that are refractory to drug therapy or where patients are intolerant of drug therapy (Howell, 2015). Policy updates: The updated ASFA guideline on therapeutic apheresis includes 14 new indications, of which 13 are relevant to this policy (Schwartz, 2016). Recommendations for several indications were changed reflecting changes in the evidence base and standards of care. Atypical hemolytic uremic syndrome (ahus) and HUS were 6

7 renamed thrombotic microangiopathy, complement-mediated and thrombotic microangiopathy, Shiga toxin-mediated, respectively. The policy and the appendix were amended with these changes. New indications include: Atopic (neuro-) dermatitis (atopic eczema), recalcitrant (category III). Cardiac neonatal lupus (III). Complex regional pain syndrome (III). Erythropoietic porphyria, liver disease (III). Hashimoto s encephalopathy, steroid-responsive encephalopathy associated with autoimmune thyroiditis (II). Hemolysis, Elevated Liver Enzymes and Low Platelets (HELLP) syndrome (III, IV). Hematopoietic stem cell transplantation, HLA desensitization (III). Hemophagocytic lymphohistiocytosis; hemophagocytic syndrome; macrophage activating syndrome (III). N-methyl D-aspartate receptor antibody encephalitis (I). Progressive multifocal leukoencephalopathy associated with nataluziamab (I). Pruritus due to hepatobiliary diseases (III). Thrombotic microangiopathy, coagulation-mediated (III). Vasculitis: hepatitis B virus polyarteritis nodasa (HBV-PAN) (II); idiopathic PAN (IV); eosinophilic granulomatosis with polyangiitis (EGPA) (III); and Behcet s disease (III). New subcategories were added to: ANCA-associated rapidly progressive glomerulonephritis (granulomatosis with polyangiitis; microscopic polyangiitis), DAH (I). Thrombotic microangiopathy, complement-mediated-factor H autoantibodies (I). Recommendations for some indications were changed as follows: Cryoglobulinemia, symptomatic/severe Downgraded from I to II. PANDAS, exacerbation Downgraded from I to II. PANDAS-Sydenham s chorea, severe Downgraded from II to III. Immune thrombocytopenia, refractory Upgraded from IV to III. Summary of clinical evidence: Citation Howell (2015) for the BCSH Content, Methods, Recommendations Key points: Apheresis Evidence-based guideline based on guidelines of the ASFA, AAN (Cortese, 2011), and the Kidney Disease: Improving Global Outcomes work group (KDIGO, 2012). Applied GRADE levels and grades of evidence (see Appendix). TPE is the main treatment in TTP and can be lifesaving. It must be initiated as soon as possible, ideally within four hours of presentation (1A). TPE is indicated for conditions listed as Category I (first-line) or Category II (second- 7

8 Citation Colvin (2015) for the AHA AMR in cardiac transplantation Cortese (2013) for the AAN Guideline: Plasmapheresis in neurologic disorders Content, Methods, Recommendations line) in the current version of the ASFA guidelines (1A to 1C depending on condition). TPE may be used as second- or third-line treatment for conditions listed as Category III in the current version of the ASFA guidelines, or for unlisted conditions where removal of a pathogenic antibody makes biological sense providing there is no published evidence that plasma exchange is ineffective or detrimental in the condition in question (1C). TPE should not be used for conditions where published evidence suggests lack of benefit or harm, such as ASFA Category IV conditions (1B). Key points: Limited clinical trials, case series, and case reports suggest benefit of TPE on survival in ABO-compatible persons with either acute AMR or, to a lesser extent, as desensitization therapy for high alloantibody levels and a positive crossmatch (at high risk of acute AMR or ABO-incompatible donor [children only]). Little support for TPE as monotherapy for the management of AMR, always reported in combination with other immunomodulatory therapies. It is reasonable for primary therapy for AMR to include IVIg, plasmapheresis, antilymphocyte antibodies, and high-dose corticosteroids Recommendation in favor of treatment or procedure being useful/effective based on some conflicting evidence from single randomized trial or nonrandomized studies (Class IIa; Level of Evidence B). Key points: Guideline based on consensus statements from the ASFA (Szczepiorkowski, 2010), AAN (Cortese, 2011), and multiple Cochrane reviews. Strongest data on efficacy and most frequently used for CIDP, Guillain-Barré syndrome, myasthenia gravis, both moderate-severe and pre-thymectomy, paraproteinemic polyneuropathies (IgG/IgA), acute multiple sclerosis and Lambert-Eaton myasthenic syndrome. References Professional society guidelines/other: Colvin MM, Cook JL, Chang P, et al. Antibody-mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management: a scientific statement from the American Heart Association. Circulation. 2015; 131(18): Cortese I, Chaudhry V, So YT, et al. Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2011; 76(3): Cortese I, Cornblath DR. Therapeutic plasma exchange in neurology: J Clin Apher. 2013; 28(1):

9 Costanzo MR, Costanzo MR, Dipchand A, et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. The Journal of Heart and Lung Transplantation. 2010; 29(8): Howell C, Douglas K, Cho G, et al. Guideline on the clinical use of apheresis procedures for the treatment of patients and collection of cellular therapy products. British Committee for Standards in Haematology. Transfus Med. 2015; 25(2): KDIGO. Summary of Recommendation Statements. Kidney Int Suppl (2011). 2012; 2(2): Schwartz J, Winters JL, Padmanabhan A, 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 sixth special issue. J Clin Apher. 2013; 28(3): 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(3): Szczepiorkowski ZM, Winters JL, Bandarenko N, et al. 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. 2010; 25(3): Peer-reviewed references: Guyatt G, Gutterman D, Baumann MH, et al. Grading strength of recommendations and quality of evidence in clinical guidelines: report from an American College of Chest Physicians task force. Chest. 2006; 129(1): CMS National Coverage Determinations (NCDs): Apheresis (Therapeutic Pheresis). CMS website. Accessed June 3, Local Coverage Determinations (LCDs): No LCDs identified as of the writing of this policy. Commonly submitted codes Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill accordingly. 9

10 CPT Code Description Comments Therapeutic apheresis; for plasma pheresis Therapeutic apheresis; with extracorporeal immunoadsorption and plasma reinfusion ICD-10 Code Description Comments C88.0 Primary macroglobulinemia (Waldenstrom) D47.2 Monoclonal gammopathy D59.1 Autoimmunic hemolytic anemia D59.3 Acute hemolytic uremic syndrome D68.61 Catastrophic antiphospholipid syndrome D89.1 Cryoglobulinemia D89.89 PANDAs E78.0 Familial hypercholesterolemia, homozygous type in persons with small blood volume. E83.01 Wilson s disease G04.90 Acute disseminated encephalomyelitis. G36.0 Acute neuromyelitis optica (Devic s syndrome) G37.8 Acute fulminant central nervous system (CNS) demyelination, G60.1 Phytanic acid storage disease (Refsum s disease). G61.0 Guillain-Barré Syndrome G61.81 Demyelinating polyneuropathy G62.9 Polyradiculoneuropathy G62.9 Chronic relapsing polyneuropathy G70.01 Acquired myasthenia gravis G70.80 Lambert-Eaton myasthenic syndrome. M05.20 Rheumatoid vasculitis M31.0 Goodpastures M31.1 Thrombotic thrombocytopenia purpura M31.1 Thrombotic microangiography M31.31 Wegener s granulomatosis M32.9 Systemic lupus erythematosus (life-threatening). M33.20 Polymyositis M34.9 Scleroderma and N05.9 Glomerulonephritis N17.9 Myeloma with acute renal failure. N26.9 Glomerulosclerosis T62.0X1 Mushroom (wild) poisoning T86.11 ABO incompatible renal transplantation-humoral rejection. HCPCS Level II Code N/A Description Comments Appendix ASFA indication categories for plasmaperesis and TPE* 10

11 Clinical indication Category GRADE** recommendation Acute inflammatory demyelinating polyneuropathy (Guillain-Barré Syndrome), alone I 1A ANCA- associated rapidly progressive glomerulonephritis (Granulomatosis with polyangiitis; microscopic polyangiitis), dialysis dependence I 1A ANCA- associated rapidly progressive glomerulonephritis (Granulomatosis with polyangiitis; microscopic polyangiitis), DAH I 1C Anti-glomerular basement membrane disease (Goodpasture s syndrome), DAH I 1C Anti-glomerular basement membrane disease (Goodpasture s syndrome), dialysis independence I 1B Chronic inflammatory demyelinating polyradiculoneuropathy I 1B Focal segmental glomerulosclerosis, recurrent in transplanted kidney I IB Hyperviscosity in monoclonal gammopathies, prophylaxis for rituximab I 1C Hyperviscosity in monoclonal gammopathies, symptomatic I 1B Liver transplantation, ABO incompatible, desensitization, live donor I 1C Myasthenia gravis, pre-thymectomy I 1C Myasthenia gravis, moderate-severe I 1B N-methyl D-aspartate receptor antibody encephalitis I 1C Paraproteinemic demyelinating polyneuropathies/chronic acquired demyelinating polyneuropathies, IgG/IgA I 1B Paraproteinemic demyelinating polyneuropathies/chronic acquired demyelinating polyneuropathies, IgM I 1C Progressive multifocal leukoenchephalopathy associated with natalizumab I 1C Renal transplantation, ABO compatible, AMR I 1B Renal transplantation, ABO compatible,desensitization, living donor, positive crossmatch due to donor specific HLA antibody I 1B Renal transplantation, ABO incompatible, desensitization, live donor I 1B Thrombotic microangiopathy, complement-mediated- factor H autoantibodies I 2C Thrombotic microangiopathy, drug associated- Ticlopidine I 2B Thrombotic thrombocytopenic purpura I 1A Wilson disease I 1C Acute disseminated encephalomyelitis II 2C Autoimmunic hemolytic anemia, severe cold agglutinin disease II 2C Catastrophic antiphospholipid syndrome II 2C Cryoglobulinemia, symptomatic/severe II 2A Famalial hypercholesterolemia, homozygotes with small blood volume II 1C Hashimoto s encephalopathy, steroid responsive encephalopathy associated with autoimmune thyroiditis II 2C HSCT, ABO incompatible, major HPC, apheresis II 2B HSCT, ABO incompatible, major HPC, marrow II 1B Lambert-Eaton myasthenic syndrome II 2C Multiple sclerosis, acute CNS inflammatory demyelinating disease II 1B Myeloma cast nephropathy II 2B Neuromyelitis optica spectrum disorders, acute II 1B Overdose, envenomation and poisoning, mushroom poisoning II 2C PANDAS, exacerbation II 1B Phytanic acid storage disease (Refsum s disease) II 2C Renal transplantation, ABO incompatible, AMR II 1B 11

12 Clinical indication Category GRADE** recommendation Systemic lupus erythematosus, severe II 2C Vasculitis, HBV-PAN II 2C Voltaged gated potassium channel antibodies, fulminant II 1C Acute inflammatory demyelinating polyneuropathy (Guillain-Barré Syndrome), post IVIG III 2C Acute liver failure III 2B ANCA- associated rapidly progressive glomerulonephritis (Granulomatosis with polyangiitis; microscopic polyangiitis), dialysis independence III 2C Anti-glomerular basement membrane disease (Goodpasture s syndrome), dialysis dependent and no DAH III 2B Aplastic anemia, pure red cell aplasia, aplastic anemia III 2C Aplastic anemia, pure red cell aplasia, pure red cell aplasia III 2C Atopic (neuro-) dermatitis (atopic eczema), recalcitrant III 2C Autoimmune hemolytic anemia, severe warm autoimmune hemolytic anemia III 2C Burn shock resuscitation III 2B Cardiac neonatal lupus III 2C Cardiac transplantation, ABO-compatible, acute desensitization III 2C Cardiac transplantation, ABO-compatible, acute AMR III 2C Chronic focal encephalitis (Rasmussen encephalitis) III 2C Coagulation factor inhibitors-autoantibody III 2C Complex regional pain syndrome, chronic III 2C Dilated cardiomyopathy, idiopathic New York Heart Association (NYHA) II-IV III 2C Erythropoietic porphyria, liver disease III 2C HELLP syndrome, postpartum III 2C Hematopoietic stem cell transplantation, HLA desensitization III 2C Hemophagocytic lymphohistiocytosis, hemophagocytic syndrome, macrophage activating syndrome III 2C Henoch-Schonlein purpura, crescentric III 2C Henoch-Schonlein purpura, severe extra-renal disease III 2C Heparin induced thrombocytopenia, pre-cardiopulmonary bypass III 2C Heparin induced thrombocytopenia, thrombosis III 2C Hypertriglyceridemic pancreatitis III 2C Immunoglobin A nephropathy, chronic progressive III 2C Immunoglobin A nephropathy, crescentic III 2B Liver transplantation, ABO incompatible, AMR (ABOi & HLA) III 2C Liver transplantation, ABO incompatible, desensitization, deceased donor III 2C Lung transplantation, AMR III 2C Multiple sclerosis, chronic progressive III 2B Nephrogenic systemic fibrosis III 2C Neuromyelitis optica spectrum disorders, maintenance III 2C Overdose, envenomation and poisoning, envenomation III 2C Overdose, envenomation and poisoning, drug overdose/poisoning III 2C PANDAS, sydenham s chorea, severe III 2B Paraneoplastic neurological syndromes III 2C Paraproteinemic demyelinating polyneuropathies/chronic acquired demyelinating polyneuropathies, multiple myeloma III 2C Paraproteinemic demyelinating polyneuropathies/chronic acquired demyelinating III 1C 12

13 Clinical indication Category GRADE** recommendation polyneuropathies, anti-myelin-associated glycoprotein (anti-mag) neuropathy Pemphigus vulgaris III 2B Post transfusion purpura III 2C Pruritus due to hepatobiliary diseases, treatment resistant III 1C Red cell alloimmunization in pregnancy, prior to intrauterine transfusion availability III 2C Renal transplantation, ABO compatible, desensitization, high panel reactive antibody, deceased donor III 2C Scleroderma (progressive systemic sclerosis) III 2C Sepsis with multi-organ failure III 2B Stiff-person syndrome III 2C Sudden sensorineural hearing loss III 2C Thrombotic microangiopathy, coagulation mediated (THBD mutation) III 2C Thrombotic microangiopathy, complement-mediated- complement factor gene mutations III 2C Thrombotic microangiopathy, complement-mediated-mcp mutations III 1C Thrombotic microangiopathy, drug associated-clopidogrel III 2B Thrombotic microangiopathy, drug associated-calcineurin inhibitors III 2C Thrombotic microangiopathy, HSCT associated, refractory III 2C Thrombotic microangiopathy, Shiga toxin-mediated Streptococcus pneumonia III 2C Thrombotic microangiopathy, Shiga toxin-mediated, severe neurological symptoms III 2C Thyroid storm III 2C Toxic epidermal necrolysis, refractory III 2B Vascularitis, Behcet s disease III 2C Vascularitis, EGPA III 1B Immune thrombocytopenia, refractory III 2C Amyloidosis, systemic IV 2C Amyotrophic lateral sclerosis IV 1C Coagulation factor inhibitors, alloantibody IV 2C Dermatomyositis or polymyositis IV 2B HELLP syndrome, antepartum IV 2C Inclusion body myositis IV 2C Paraproteinemic demyelinating polyneuropathies/chronic acquired demyelinating polyneuropathies, multifocal motor neuropathy IV 1C Polyneuropathy, organomegaly, endocrinopathy, M Protein and skin changes (POEMS) syndrome IV 1C Psoriasis IV 2C Renal transplantation, ABO incompatible, Group A2/A2B into B, deceased donor IV 1B Schizophrenia IV 1A Systemic lupus erythematosus, nephritis IV 1B Thrombotic microangiopathy, drug associated-gemcitabine IV 2C Thrombotic microangiopathy, drug associated-quinine IV 2C Thrombotic microangiopathy, Shiga toxin-mediated, absence of severe neurologic symptoms IV 1C Vacularitis, idiopathic PAN IV 1B *Adapted from Schwartz (2016). 13

14 **GRADE, Grading of Recommendations Assessment, Development and Evaluation system. Adapted from Guyatt (2006). Grade 1A. Strong recommendation, high-quality evidence. Grade 1B. Strong recommendation, moderate quality evidence. Grade 1C. Strong recommendation, low-quality or very low-quality evidence. Grade 2A. Weak recommendation, high quality evidence. Grade 2B. Weak recommendation, moderate-quality evidence. Grade 2C. Weak recommendation, low-quality or very low-quality evidence. Note: Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome that can result from a number of etiologies, and not a single disease entity. The majority of patients who present with RPGN are ANCApositive with minimal immune deposits in the glomerulus. To a lesser extent, RPGN may present with granular deposits of various immune complexes or linear deposits of IgG due to autoantibodies to Type IV collagen. The specific category of RPGN should be identified, as TPE treatment protocols and responses differ among the three categories (Schwartz, 2016). 14