The New Approach to Assignment of ASFA Categories Introduction to the Fourth Special Issue: Clinical Applications of Therapeutic Apheresis

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1 Journal of Clinical Apheresis 00: (2007) The New Approach to Assignment of ASFA Categories Introduction to the Fourth Special Issue: Clinical Applications of Therapeutic Apheresis Zbigniew M. Szczepiorkowski, 1 * { Beth H. Shaz, 2 * Nicholas Bandarenko, 3 * and Jeffrey L. Winters 4 * 1 Transfusion Medicine Service, Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 2 Department of Pathology and Laboratory Medicine, Grady Memorial Hospital, Emory University, Atlanta, Georgia 3 Department of Pathology and Laboratory Medicine, University of North Carolina Hospitals, Chapel Hill, North Carolina 4 Division of Transfusion Medicine, Mayo Clinic, Rochester, Minnesota The American Society for Apheresis (ASFA) Apheresis Applications Committee is responsible for a review and categorization of indications for therapeutic apheresis. The results of the review process were previously published in 1986, 1993, and 2000 as the ASFA Special Issues. The ASFA categories consist of categories I through IV, and category P (pending). This article describes the novel methodology, based on structured systematic review of the published literature, used to assign categories for indications for therapeutic apheresis. This is the first time each entity is presented as a fact sheet, which summarizes the evidence for the use of therapeutic apheresis. A detailed description of the fact sheet format and the individual fact sheets for categories I through III and category P are presented in the main article of this Special Issue. The diseases assigned to category IV are discussed in a separate article in this issue. Information on how the Apheresis Applications Committee proposes to include new diseases for category assignment is also provided. J. Clin. Apheresis. 00: , 2007 VC 2007 Wiley-Liss, Inc. Key words: apheresis; plasma exchange; immunoadsorption; leukocytapheresis; photopheresis; categories INTRODUCTION It is with great pleasure that we present you the American Society for Apheresis (ASFA) Special Issue 2007 (aka the 4th Edition of the ASFA Special Issue). After more than a year of engaging work and the introduction of significant changes to the ASFA Special Issue, we believe that this document will appeal to practitioners of apheresis medicine. This is also the first step in linking specific ASFA Categories with analysis based on the quality of evidence and not solely the number of publications in the literature. This publication consists of the Introduction, which contains the discussion of our methodology and summarizes the ASFA Categories for 2007; the Main article which compiles all 53 ASFA Fact Sheets; the article on ASFA Category IV indications; and two guideline documents prepared by the Apheresis Applications Committee on credentialing therapeutic apheresis (TA) providers and documentation of the TA procedures. The articles are intended to be user friendly. The main change in comparison with previous editions of the Special Issue is the introduction of the comprehensive ASFA Fact Sheet, a format designed to summarize and condense the available medical literature pertaining to VC 2007 Wiley-Liss, Inc. This document contains information prepared by the American Society for Apheresis (ASFA) for the apheresis community and those who request the use of therapeutic apheresis. Although due care has been used in the preparation of this document, ASFA makes no representation or warranty, express or implied, that it is free from errors or omissions, or that it is exhaustive, and expressly disclaims all warranties, including but not limited to, warranties as to the information s quality or fitness for a particular purpose. The information contained herein is not intended to supplant the clinical judgment of qualified medical professionals. ASFA and its directors, officers, employees, members, representatives and agents accept no liability for any loss, cost, expense, injury or damages, whether direct, indirect, incidental, consequential, special or other, arising from the application of the information contained in this document for patient care or any other use. The accuracy of the information contained herein is subject to changes in circumstances after the time of publication. ASFA accepts no responsibility for the accuracy and reliability of information provided by third parties. *All authors contributed equally to this publication. { Correspondence to: Zbigniew M. Szczepiorkowski, Transfusion Medicine Service, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH ziggy@dartmouth.edu Published online in Wiley InterScience ( DOI: /jca.20134

2 2 Szczepiorkowski et al. TABLE I. Indications for Therapeutic Apheresis ASFA Categories a Category I II III IV Description Category I includes diseases for which TA is standard and acceptable, either as a primary therapy or a valuable first-line adjunct therapy. (The perception of efficacy in these disorders is usually based on well-designed randomized controlled trials or on a broad and non-controversial base of published experience.) Note that this designation need not imply that TA is mandatory in all cases. Category II denotes diseases for which TA is generally accepted but considered to be supportive or adjunctive to other, more definitive treatments, rather than a primary first-line therapy. (Randomized controlled studies are available for some of these disorders, but in others the literature contains only small series or informative case studies.) Category III diseases are those in which there is a suggestion of benefit for which existing evidence is insufficient, either to establish the efficacy of TA or to clarify the risk/benefit (or sometimes the cost/benefit) ratio associated with TA. Included are disorders in which controlled trials have produced conflicting results or for which anecdotal reports are too few or too variable to support an adequate consensus. Therapeutic apheresis may reasonably be used in such patients when conventional therapies do not produce an adequate response or as part of an IRB-approved research protocol. Category IV indicates disorders for which controlled trials have not shown benefit or anecdotal reports have been discouraging. TA for these disorders is discouraged and should be carried only in the context of an IRB-approved research protocol. P Category P (pending) includes diseases which can be treated by therapeutic apheresis using devices that are not available in the US and/or do not have FDA clearance. This category is generally assigned to those diseases where the devices are being studied in Phase III trials in the US. a The description of categories as presented in the 3rd Edition of the Special Issue except for new category P which has been added [1]. TABLE II. Level of Evidence Used in the ASFA Special Issue 2007 a Evidence grade Evidence quality Type I Obtained from at least one properly designed randomized controlled trial Type II-1 Obtained from a well-designed controlled trials without randomization Type II-2 Obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group Type II-3 Obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments could also be regarded as this type of evidence Type III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees a Adopted from the criteria used by the University HealthSystem Consortium [8]. the treatment of a disease by apheresis into a succinct review focusing on practical issues for the apheresis practitioner. In addition, these sheets can also be used as an educational tool for physicians requesting therapeutic apheresis procedures and for patients who want to learn more about the basis of TA in treating their disease. Table I defines the ASFA Categories. We also acknowledge that since the publication of the 3rd edition of the Special Issue there have been at least two excellent textbooks summarizing knowledge on therapeutic apheresis [2,3]. Thus, we did not provide background information in this article which can be easily identified in those textbooks with a few minor exceptions when we believed it was critical for better understanding of our intent. ASFA FACT SHEET A template was established with the intent to facilitate review, updating of the disease categorization, and to provide uniform analysis of the published literature. The template, called the ASFA Fact Sheet, includes such information as disease incidence, number of patients reported to have been treated, types of reports appearing in the medical literature, level of evidence for TA use, general disease description and treatment, rationale for apheresis, recommended apheresis regimen including frequency and replacement volume, and parameters for discontinuation. The information provided in the fact sheet format is comprehensive but limited in length to facilitate its use as a quick reference. A detailed description of the ASFA Fact Sheet is provided in the main article of this Special Issue [4]. EVIDENCE BASED APPROACH In the ASFA Special Issue 2000, Dr. Vamvakas eloquently discussed the ways medical literature can be analyzed and interpreted [5]. We have attempted in the ASFA Special Issue 2007 to incorporate evidence based

3 Therapeutic Apheresis ASFA Categories 3 Fig. 1. The ASFA Category I III and P and the quality of evidence in the reviewed literature. medicine into the well defined and widely accepted ASFA Categories. There are various systems to grade the quality of evidence and strength of recommendations [6,7]. We adopted the evidence quality criteria defined by the University HealthSystem Consortium (UHC) for the sole purpose of grading the level of available evidence (Table II) [8]. While there are other more sophisticated systems to grade evidence, such as one utilized by the Agency for Health Care Policy and Research, at this point in time we selected the well established and simpler approach. It is quite likely that in the future publications of the ASFA Special Issue, we will consider more sophisticated approaches which incorporate quality of evidence as suggested by different professional organizations [6,7]. Figure 1 illustrates the relationship between ASFA category as assigned in the ASFA Special Issue 2007 and the quality of evidence in the published literature. These data were compiled after the process of writing of the fact sheets was complete (see later). It can be noted that a lower quality of evidence is more likely to result in an indication being assigned category III. The findings are not completely unexpected as the level of evidence only defines the quality of data used to derive ASFA categories. High level of evidence, such as type I, is more likely to be associated with a higher level of confidence in either applying (ASFA Category I) or not performing (ASFA Category IV) therapeutic apheresis as a treatment modality. METHODOLOGY FOR ASFA CATEGORIES ASSIGNMENT IN 2007 AND IN THE FUTURE A novel process for ASFA category assignment has been developed to facilitate accuracy and timely future updates for therapeutic apheresis indications. The committee based approach is comprehensive and systematic in assembling objective evidence for disease indications, with emphasis on the quality of evidence. A Clinical Categories Subcomittee consisting of 10 ASFA members and the ASFA executive director was established. The group was asked to review, revise, and amend indications for therapeutic apheresis. The process of developing new indications consisted of five steps (Fig. 2). Step I created a list of diseases to be included. Step II assigned each of the working group members 5 8 diseases to review. At a minimum, the review consisted of identifying all articles published in the English language which described the use of therapeutic apheresis. In addition, all abstracts presented since 2000 at ASFA, AABB, and ASH annual meetings were included in the analysis, as well as abstracts presented in the meetings of other professional organizations, when appropriate. Step III consisted of circulating the first draft of the submission to two other members of the subcomittee for editorial comments. On the basis of these comments the author created Draft II. In step IV, an independent non-apheresis expert in the relevant medical specialty reviewed Draft II. Input from this person was incorporated into Draft III. In step V, all fact sheets were finalized and each disease was assigned an ASFA category at a face to face meeting of the subcommittee in spring The category assignment was based upon the strength of the evidence and determined by anonymous votes of all subcommittee members. There was a thorough discussion with a final consensus or anonymous voting on the diseases without a clear category assignment. When the strength of evidence was considered, the members of the subcommittee were encouraged to use McLeod s Criteria which are summarized in a modified form in Table III [9]. We encourage the practitioners of apheresis medicine to use these criteria when considering the use of therapeutic apheresis in a medical condition which is not categorized by ASFA. The subcommittee also devised a novel approach for updating indications and categories between publications of ASFA Special Issues. This new process is depicted in Figure 3 and will be initiated by a request for a change of the existing ASFA category or a request for the generation of a new fact sheet. First, there is a screening process by an assigned subcommittee member to determine if there is sufficient new information to warrant a more thorough review and generation of a new or modified fact sheet. The new or modified fact sheet will undergo the same rigorous review as the ones published in the Special Issue. The ASFA category will be assigned by the same process to the new or modified fact sheet. The new or modified fact sheet will then be published in the Journal of Clinical Apheresis once finalized. In addition, these new or modified fact sheets will be then added to the next edition of the Special Issue. Table IV summarizes all fact sheets and ASFA indications categories I through III and category P. The

4 4 Szczepiorkowski et al. Fig. 2. Systematic approach to category assignment and ASFA Fact Sheet generation used in the ASFA Special Issue TABLE III. Modified McLeod s Criteria for Evaluation of Efficacy of Therapeutic Apheresis [9] Evidence McLeod s criteria Explanation Mechanism Plausible pathogenesis The current understanding of the disease process supports a clear rationale for the use of therapeutic apheresis modality. Correction Better blood The abnormality, which makes therapeutic apheresis plausible, can be meaningfully corrected by its use. Clinical effect Perkier patients There is a strong evidence that therapeutic apheresis confers benefit that is clinically worthwhile, and not just statistically significant.

5 Therapeutic Apheresis ASFA Categories 5 Fig. 3. A proposed review process for new indications and/or updating previously categorized indications for therapeutic apheresis. table also compares the ASFA Special Issue 2007 (4th Edition) with 2000 (3rd Edition) for those who would like to see the changes we introduced. The table for category IV indications is found in the category IV indication article of this special issue [10]. GENERAL CONSIDERATIONS As mentioned in the introduction to this article, there are new textbooks in the field of apheresis medicine, which users of the Special Issue may find useful. The new format of the Special Issue restricted the amount

6 6 Szczepiorkowski et al. TABLE IV. Indication Categories for Therapeutic Apheresis Disease group / Name / Condition TA Modality ASFA 2007 ASFA 2000 AUTOIMMUNE Catastrophic antiphospholipid syndrome Cryoglobulinemia Plasma exchange I II Pemphigus vulgaris Extracorporeal photopheresis III NC Systemic lupus erythematosus Manifestations other than nephritis Nephritis Plasma exchange IV NC HEMATOLOGIC ABO incompatible hematopoietic progenitor cell transplantation Plasma exchange II II Aplastic anemia; pure red cell aplasia Autoimmune hemolytic anemia: warm autoimmune hemolytic anemia: cold agglutinin disease Babesiosis Severe Erythrocytapheresis II III Coagulation factor inhibitors Immunoadsorption III NC Plasma exchange III II Cutaneous t cell lymphoma; mycosis fungoides Erythrodermic Extracorporeal photopheresis I I Non-erythrodermic Extracorporeal photopheresis IV NC Erythrocytosis; polycythemia vera Symptomatic Erythrocytapheresis II II Graft-versus-host disease Skin Extracorporeal photopheresis II NC Non-skin Extracorporeal photopheresis III NC Hyperleukocytosis Leukostasis Leukocytapheresis I I Prophylaxis Leukocytapheresis III NC Hyperviscosity in monoclonal gammopathies Plasma exchange I II Idiopathic thrombocytopenic purpura Refractory Immunoadsorption II II Refractory or non-refractory Plasma exchange IV NC Malaria Severe Erythrocytapheresis II III Myeloma and acute renal failure Plasma exchange III II Posttranfusion purpura Plasma exchange III I Red cell alloimmunization in pregnancy Plasma exchange II III Sickle cell disease Life and organ threatening Erythrocytapheresis I I Stroke prophylaxis Erythrocytapheresis II NC Prevention of iron overload Erythrocytapheresis II NC Thrombocytosis Symptomatic Thrombocytapheresis II I Prophylactic or secondary Thrombocytapheresis III NC Thrombotic thrombocytopenic purpura Plasma exchange I I METABOLIC Acute liver failure Familial hypercholesterolemia Homozygotes Selective Removal I I Heterozygotes Selective Removal II I Plasma exchange II II

7 Therapeutic Apheresis ASFA Categories 7 TABLE IV. (Continued) Disease group / Name / Condition TA Modality ASFA 2007 ASFA 2000 Hypertriglyceridemic pancreatitis Overdose and poisoning Mushroom poisoning Plasma exchange II III Other compounds Phytanic acid storage disease (Refsum s disease) Plasma exchange II I Sepsis Thyrotoxicosis MISCELLANEOUS Dilated cardiomyopathy Immunoadsorption P NC Inflammatory bowel disease Adoptive cytapheresis P NC Macular degeneration, age-related Membrane differential filtration P NC NEUROLOGICAL Acute disseminated encephalomyelitis Acute inflammatory demyelinating polyneuropathy (Guillain-Barre syndrome) Plasma exchange I I Chronic inflammatory demyelinating polyradiculoneuropathy Plasma exchange I I Lambert-Eaton myasthenic syndrome Plasma exchange II II Multiple sclerosis Acute CNS inflammatory demyelinating disease Plasma exchange II II Devic s syndrome Chronic progressive Myasthenia gravis Plasma exchange I I Paraneoplastic neurologic syndromes Immunoadsorption III NC Paraproteinemic polyneuropathies IgG/IgA Plasma exchange I I IgM Plasma exchange II II Multiple myeloma IgG/IgA/IgM Immunoadsorption III III Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; Sydenham s chorea Severe PANDAS Plasma exchange I II Severe SC Plasma exchange I II Rassmussen s encephalitis Plasma exchange II III Stiff-person syndrome RENAL ANCA-associated rapidly progressive glomerulonephritis (Wegener s granulomatosis) Plasma exchange II II Anti-glomerular basement membrane disease (Goodpasture s syndrome) Plasma exchange I I Focal segmental glomerulosclerosis Primary Secondary Hemolytic uremic syndrome; thrombotic microangiopathy; transplant associated microangiopathy Idiopathic HUS Other Transplant associated microangiopathy Diarrhea associated pediatric Plasma exchange IV NC

8 8 Szczepiorkowski et al. TABLE IV. (Continued) Disease group / Name / Condition TA Modality ASFA 2007 ASFA 2000 Rapidly progressive glomerulonephritis Plasma exchange III II Renal transplantation: antibody mediated rejection; HLA desensitization Antibody mediated rejection Plasma exchange II NC HLA desensitization Plasma exchange II III RHEUMATIC Rheumatoid arthritis, refractory Immunoadsorption II II Scleroderma (progressive systemic sclerosis) Extracorporeal photopheresis IV NC TRANSPLANTATION ABO incompatible solid organ transplantation Kidney Plasma exchange II NC Heart (infants) Plasma exchange II NC Liver Heart transplant rejection Prophylaxis Extracorporeal photopheresis I III Treatment Extracorporeal photopheresis II III Lung transplant Extracorporeal photopheresis III NC Abbreviations: NC not-categorized; TA therapeutic apheresis; for categories explanation see Table I. Note: Category IV indications are listed here only when another therapeutic modality for the listed disease has category indication I, II, III or P. All category IV indications are discussed separately in this issue [10]. For full description of disease entities and explanation for assigned category please refer to the main article in this Special Issue [4]. TABLE V. General Issues to be Considered When Evaluating a New Patient for Initiation of Therapeutic Apheresis General Rationale a Impact Technical issues a Therapeutic plan a Clinical and/or laboratory end-points a Description Based on the established/presumptive diagnosis and history of present illness the discussion could include the proposed mechanism for the procedure, brief account of the results of published studies, and patient-specific risks from the procedure. The effect of therapeutic apheresis on comorbidities and medications (and vice-versa) should be considered. The technical aspects of therapeutic apheresis such as type of anticoagulant, replacement fluid, vascular access, and volume of whole blood processed (e.g., number of plasma volumes exchanged) should be addressed. Total number and/or frequency of therapeutic apheresis procedures should be addressed. The clinical and/or laboratory parameters should be established to monitor effectiveness of the treatment. The criteria for discontinuation of therapeutic apheresis should be discussed where appropriate. Timing and location The acceptable timing of initiation of therapeutic apheresis should be considered based on clinical considerations (e.g., medical emergency, urgent, or routine). The location where the therapeutic apheresis will take place should be also addressed (e.g., intensive care unit, medical unit, operating room, or outpatient setting). If the timing appropriate to the clinical condition and urgency level cannot be met, a transfer to a different facility should be considered based on the clinical status of the patient. Note: The above issues should be considered in addition to a routine note addressing patient s history, review of systems, and physical examination. a The ASFA Fact Sheet for the specific disease addresses these issues. of information that could be represented in each fact sheet and, therefore, focused on information that would be most helpful to the readers. In Table V, we suggest information to be included in a consultation note prior to performing a TA procedure. This standard approach to consultation may be helpful to the readers who have less experience in TA. Also some of the issues related to specific diseases are clearly addressed in those disease specific fact sheets.

9 Therapeutic Apheresis ASFA Categories 9 TABLE VI. Definitions of Various Apheresis Procedures Procedure/term Apheresis Extracorporeal photopheresis (ECP) Erythrocytapheresis (RBC exchange) Filtration selective removal Immunoadsorption (IA) LDL Apheresis Leukocytapheresis (LCP) Plasma exchange (TPE) Plasmapheresis Plateletapheresis Therapeutic apheresis (TA) Thrombocytapheresis Definition A procedure in which blood of the patient or donor is passed through a medical device which separates out one or more components of blood and returns remainder with or without extracorporeal treatment or replacement of the separated component. A therapeutic procedure in which buffy coat, separated from patient s blood, is treated extracorporeally with a photoactive compound (e.g., psoralens) and exposed to ultraviolet A light and subsequently reinfused to the patient during the same procedure. A therapeutic procedure in which blood of the patient is passed through a medical device which separates red blood cells from other components of blood, the red blood cells are removed, and replaced with either donor red blood cells alone and/or colloid solution. A procedure which uses a filter to remove components from the blood based upon size. Depending upon the pore size of the filters used, different components can be removed. Filtration based instruments can be used to perform plasma exchange or LDL apheresis. They can also be used to perform donor plasmapheresis where plasma is collected for transfusion or further manufacturing. A therapeutic procedure in which plasma of the patient, after separation from the blood, is passed through a medical device which has a capacity to remove immunoglobulins by specifically binding them to the active component (e.g., Staphylococcal protein A) of the device. The selective removal of low density lipoproteins from the blood with the return of the remaining components. A variety of instruments are available which remove LDL cholesterol based upon charge (dextran sulfate and polyacrylate), size (double-membrane filtration), precipitation at low ph (HELP), or immunoadsorption with anti-apo B-100 antibodies. A procedure in which blood of the patient or the donor is passed through a medical device which separates out white blood cells (e.g. leukemic blasts or granulocytes), collects the selected cells and returns remainder of the patient s or the donor s blood with or without addition of replacement fluid such as colloid and/or crystalloid solution. This procedure can be used therapeutically or in preparation of blood components. A therapeutic procedure in which blood of the patient is passed through a medical device which separates out plasma from other components of blood, the plasma is removed and replaced with a replacement solution such as colloid solution (e.g., albumin and/or plasma) or combination of crystalloid/colloid solution. A procedure in which blood of the patient or the donor is passed through a medical device which separates out plasma from other components of blood and the plasma is removed (i.e. less than 15% of total plasma volume) without the use of replacement solution. A procedure in which blood of the donor is passed through a medical device which separates out platelets, collects the platelets and returns remainder of the donor s blood. This procedure is used in preparation of blood components (e.g., apheresis platelets). A therapeutic procedure in which a blood of the patient is passed through an extracorporeal medical device which separates components of blood to treat a disease. This is a general term which includes all apheresis based procedures used therapeutically. A therapeutic procedure in which blood of the patient is passed through a medical device which separates out platelets, removes the platelets and returns remainder of the patient s blood with or without addition of replacement fluid such as colloid and/or crystalloid solution. An area of potential concern for the apheresis practitioner is the replacement fluid used during plasma exchange. If stated in the fact sheet that plasma exchange is performed daily, plasma may be indicated as part of replacement fluid to prevent severe coagulopathy from repetitive removal of coagulation factors through serial therapeutic plasma exchange (TPE). Additionally, maintaining the fibrinogen level >100 mg/dl is typically recommended to prevent increase risk of bleeding. In many instances, plasma supplement can be given toward the end of procedure. Lastly, issues related to the timing of procedures, such as emergency (within hours), urgent (within a day), and routine, are not addressed directly in the fact sheets. The importance of therapeutic apheresis in the treatment of a specific disease is addressed in detail. Because every patient is unique and there is a wide spectrum of presentation and progression for various diseases and conditions, the subcommittee felt that categorizing diseases and disorders in this way was not appropriate. The patient s clinical condition and situation should be considered when deciding the timing of

10 10 Szczepiorkowski et al. treatment. This determination should be made through consultation between the requesting physician and the medical director of the apheresis unit using appropriate medical judgment. The subcommittee did feel that diseases that should be treated emergently, i.e., in the middle of the night if warranted, are thrombocytopenic thrombotic purpura, acute chest syndrome in sickle cell disease, thrombocytosis, hyperleukocytosis, hyperviscosity, and malaria. These are life threatening conditions where therapeutic apheresis is the primary mode of acute treatment. GLOSSARY Therapeutic apheresis procedures considered in this publication and included in the fact sheets are therapeutic plasma exchange (TPE), erythrocytapheresis, thrombocytapheresis, leukocytapheresis, extracorporeal photopheresis (ECP), immunadsorption (IA), selective removal methods, adoptive cytapheresis, and membrane differential filtration. We thought that it would be helpful to apheresis medicine community to agree on definitions of apheresis procedures. We attempted to summarize definitions of most commonly performed procedures in Table VI. ACKNOWLEDGMENTS We are greatly indebted to Drs. Chester Andrzejewski (Baystate Medical Center, Springfield, MA), Harvey G. Klein (National Institutes of Health, Bethesda, MD), Bruce C. McLeod (Rush Presbyterian, St. Luke s Medical Center, Chicago, IL), Thomas Price (Puget Sound Blood Center, Seattle, WA), James Smith (Oklahoma Blood Institute, Oklahoma City, OK), and Ronald G. Strauss (University of Iowa, Iowa City, IA) for their participation in the thoughtful and thorough review of the ASFA Fact Sheets. Their comments and suggestions were invaluable and enhanced the quality of the final publication. We are honored that the three prior editors of the ASFA Special Issues, Drs. Klein, McLeod, and Strauss, participated in the review. We are grateful to our families for their unwavering support during the process of preparation of the ASFA Special Edition The members of the subcommittee on Clinical Categories are Zbigniew M. Szczepiorkowski, MD, PhD (Chair), Nicholas Bandarenko, MD, Haewon C. Kim, MD, Michael L. Linenberger, MD, Marisa B. Marques, MD, Ravindra Sarode, MD, Joseph Schwartz, MD, Beth H. Shaz, MD, Robert Weinstein, MD, Ashka Wirk, MBA, and Jeffrey L. Winters, MD. REFERENCES 1. McLeod BC. Introduction to the third special issue: clinical applications of therapeutic apheresis. J Clin Apher 2000;15: McLeod BC, Crookston K, Eder A, King K, Kiss J, Sarode R, Winters JL. Therapeutic Apheresis. A Physician s Handbook.- Triulzi DJ, editor. Bethesda, MD: AABB; p. 3. McLeod BC, Price TH, Weinstein R. Apheresis: Principles and Practice. Bethesda, MD: AABB Press; pp. 4. Szczepiorkowski ZM, Bandarenko N, Kim HC, Linenberger ML, Marques MB, Sarode R, Schwartz J, Shaz BH, Weinstein R, Wirk A, Winters JL. Guidelines on the use of thereapeutic apheresis in clinical practice evidence based approach from the Clinical Applications Committee of the American Society for Apheresis. J Clin Apheresis 2007;22:XXX XXX. 5. Vamvakas EC. Evaluation of clinical studies of the efficacy of therapeutic apheresis. J Clin Apheresis 2000;15: Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, Guyatt GH, Harbour RT, Haugh MC, Henry D, Hill S, Jaeschke R, Leng G, Liberati A, Magrini N, Mason J, Middleton P, Mrukowicz J, O Connell D, Oxman AD, Phillips B, Schunemann HJ, Edejer TT, Varonen H, Vist GE, Williams JW Jr., Zaza S. Grading quality of evidence and strength of recommendations. BMJ 2004;328: Atkins D, Eccles M, Flottorp S, Guyatt GH, Henry D, Hill S, Liberati A, O Connell D, Oxman AD, Phillips B, Schunemann H, Edejer TT, Vist GE, Williams JW Jr. Systems for grading the quality of evidence and the strength of recommendations I: critical appraisal of existing approaches The GRADE Working Group. BMC Health Serv Res 2004;4: University HealthSystem Consortium Clinical Practice Advancement Center. Technology Assessment: Intravenous Immunoglobulin Preparations. Oak Brook, IL. University HealthSystem Consortium; pp. 9. McLeod BC. An approach to evidence-based therapeutic apheresis. J Clin Apher 2002;17: Shaz BH, Linenberger ML, Szczepiorkowski ZM, Bandarenko N, Kim HC, Marques MB, Sarode R, Schwartz J, Weinstein R, Wirk A, Winters JL. Category IV ASFA Indications for Therapeutic Apheresis. J Clin Apheresis 2007;22:XXX XXX.