Winters, Jeffrey L.

The decision to treat a patient with therapeutic apheresis depends on multiple factors, such as what does the patient most likely have, is the diagnosis amenable to apheresis treatment, what is the harm‐versus‐benefit ratio of apheresis treatment in this patient, and what are the internal and external issues associated with receiving apheresis treatment? The “ G uidelines on the U se of T herapeutic A pheresis in C linical P ractice— E vidence‐based A pproach from the Writing C ommittee of the A merican S ociety for A pheresis” addresses these issues and helps aid in clinical decision making. The development and application of these G uidelines as well as potential new applications will be discussed in this article.

SummaryThe initial description of therapeutic plasma exchange (TPE) in an animal model was published almost 100 years ago. Since that time, this treatment has been applied to a wide variety of diseases but limited research has been published examining the mechanisms of action ofTPE. The therapeutic effects ofTPEcould include the removal of pathological substances from the blood, such as monoclonal paraproteins and autoantibodies, as well as the replacement of deficient plasma components when plasma is used as a replacement fluid. Beyond these potential mechanisms, other possible mechanisms include possible alterations in lymphocyte proliferation and function that could sensitize these cells to immunosuppressant and chemotherapeutic agents and alterations in the immune system including changes inBandTcell numbers and activation, increasedTsuppressor function, and alteration inT‐helper cell type 1/2 (Th1/Th2) ratio. Much remains unknown about the mechanisms of action ofTPE, indicating a need for basic research into this therapy.

The American Society for Apheresis (ASFA) conducted a 1 day consensus conference on Thrombotic Thrombocytopenic Purpura (TTP) during its annual meeting in Atlanta, GA, on April 10, 2012. The authors of this article, a subcommittee of ASFA's Clinical Applications Committee, developed several questions with regard to definitions, classification, pathophysiology, diagnosis, management, and future research in TTP. These questions were provided to the seven invited speakers who are the experts in the field of TTP. Two moderators conducted the proceedings of the conference which was attended by more than 100 participants. After each presentation, there was an open discussion that included moderator‐selected written questions submitted by the audience. A medical writer‐generated transcript of the proceedings as well as each presentation was made available to the authors. Each summary was reviewed and approved by the respective speaker before submission of this article. The subcommittee also developed seven key questions for blinded, electronic polling conducted by the moderators to generate a consensus amongst the speakers. This article includes these presentation summaries as well as results of the electronic poll. J. Clin. Apheresis 29:148–167, 2014. © 2013 The Authors. Journal of Clinical Apheresis Published by Wiley Periodicals, Inc.

The American Society for Apheresis (ASFA) JCA Special Issue Writing Committee is charged with reviewing, updating and categorizating indications for therapeutic apheresis. Beginning with the 2007 ASFA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence‐based approach in the grading and categorization of indications. This Sixth Edition of the ASFA Special Issue has further improved the process of using evidence‐based medicine in the recommendations by consistently applying the category and GRADE system definitions, but eliminating the “level of evidence” criteria (from the University HealthCare Consortium) utilized in prior editions given redundancy between GRADE and University HealthCare Consortium systems. The general layout and concept of a fact sheet that was utilized in the Fourth and Fifth Editions, has been largely maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. This article consists of 78 fact sheets (increased from 2010) for therapeutic indications in ASFA categories I through IV, with many diseases categorized having multiple clinical presentations/situations which are individually graded and categorized. J. Clin. Apheresis 28:145–284, 2013. © 2013 Wiley Periodicals, Inc.

Case ReportA 50‐year‐old male with T‐cell lymphoma presented for autologous peripheral blood stem cell transplantation. After granulocyte–colony‐stimulating factor (G‐CSF) mobilization, his peripheral blood CD34+ cell count was 166 × 106/L on the day before collection, which predicted a high yield of CD34+ cells in the apheresis product. The first two collections had yields much lower than expected, triggering an investigation and changes to the apheresis collection methods since mobilization appeared adequate from the peripheral CD34+ values.ResultsChanges to the apheresis collection variables and instrumentation did not improve the yields in the next three collections. The laboratory investigation demonstrated that there was an interfering substance in the patient's plasma that was causing falsely high peripheral blood CD34+ cell values and that the low CD34+ cell yields in the collections were consistent with the actual peripheral blood CD34+ cell value. Based on this finding and after discussion with the clinical service, the patient then received plerixafor to increase the number of circulating CD34+ cells before Collections 6 and 7. The patient went on to achieve the target CD34+ cell dose and subsequently underwent a successful autologous transplant with full hematopoietic engraftment.ConclusionThis case demonstrates the importance of timely and critical review of laboratory results in the context of the specific patient. This case exemplifies how diligent review of laboratory results and open communication among the various teams can positively affect patient outcomes.

BackgroundThe AMICUS (Fenwal, Inc.) was cleared in the United States for platelet (PLT) and plasma collection in 1996 with subsequent clearances for the collection of other blood products. Although not previously used for therapeutic plasma exchange (TPE), new disposables, software, and hardware were developed to enable TPE on the AMICUS.Study Design and MethodsA multicenter, randomized, nonblinded, crossover paired treatment protocol was performed. Thirty patients with orders for at least two TPE procedures were randomly assigned to the AMICUS or the COBE Spectra (TerumoBCT) for the first treatment. Each patient was crossed over to the other device using the same procedure settings from the first procedure. The primary objective compared efficiency of plasma removal (EPR) with secondary objectives of comparing PLT and hemoglobin (Hb) waste plasma content, coagulation factor and complement activation, fluid balance tracking accuracy, procedure length, and adverse events.ResultsThe EPR for the AMICUS (81.9 ± 7.62%) was superior to that of the COBE Spectra (75.2 ± 6.29%; p = 0.00001). The AMICUS also demonstrated statistically higher fluid balance accuracy (99.84%) compared to that of the COBE Spectra (98.83%; p < 0.0001) and a statistically shorter procedure time (103.9 ± 30.8 vs. 110.5 ± 27.1 min, p < 0.001). No significant differences with regard to PLT and Hb content in the waste plasma, change in patient PLT count, or changes in markers of coagulation and complement cascade activation were seen. Frequency and severity of adverse reactions were similar.ConclusionThe AMICUS separator can effectively perform TPE. The AMICUS demonstrated superior plasma removal efficiency compared to the COBE Spectra with no evidence of significant differences in PLT removal, hemolysis, and coagulation or complement activation.

The literature on the use of therapeutic apheresis is often criticized for the preponderance of low to very low quality evidence. Shehata et al. examined the apheresis literature published between 1976 and 1999 and found a lack of randomized controlled trials with those identified demonstrating significant limitations. To determine if this has improved, MEDLINE was searched for randomized controlled therapeutic apheresis trials. In addition, the Clinicaltrials.gov database was also searched for actively recruiting randomized controlled therapeutic apheresis trials. The results revealed that the total and average number of publications per year examining therapeutic apheresis has increased substantially in the period 2000–2012 compared to 1976–1999. This was associated with a small increase in the average number of randomized controlled trials reported each year, but these trials represented a smaller percentage of the therapeutic apheresis literature published compared to the 1976–1999 time range. The reported trials continued to have very small numbers of enrolled patients raising questions about their ability to determine whether apheresis represents an effective therapy. Finally, according to the Clinicaltrials.gov database, a small number of randomized controlled trials of therapeutic apheresis are enrolling patients. Despite an increasing emphasis on evidence‐based medicine and the need for quality randomized controlled clinical trials, there is still a lack of such trials when it comes to therapeutic apheresis. There continues to be a need for more and better designed randomized trials in therapeutic apheresis. J. Clin. Apheresis 28:48–55, 2013. © 2013 Wiley Periodicals, Inc.

BackgroundIdentifying antibodies to HLA (anti‐HLA) by solid‐phase assays is used to screen blood donors to mitigate transfusion‐related acute lung injury risk. Various cutoffs for detection assays have been proposed in the literature; however, these do not take into consideration lot‐to‐lot variability of commercially available assays.Study Design and MethodsSamples from 93 nontransfused males were tested using five different lots of a multiplex bead‐based anti‐HLA detection kit. A subset of 17 samples was tested on 5 days using a single lot. An additional 96 samples from donations with varied anti‐HLA levels were tested using kits from two different lots. Results were reported as a normalized background (NBG) ratio.ResultsFor the 93 nontransfused donors, NBG values generated using the reference lot were significantly higher than those obtained with three of the four comparator lots. However, for the 96 samples with low‐, moderate‐, and higher‐level anti‐HLA, Class I (CL‐I) values were 1.4 times lower and Class II (CL‐II) values were 1.2 times lower using the reference versus comparator lot. For CL‐I antibodies the between‐lot standard deviation (SD) was 1.36 (95% confidence interval [CI], 1.19‐1.60), while the between‐day SD was 1.27 (95% CI, 1.08‐1.52). Similarly, for CL‐II antibodies the between‐lot SD was 0.81 (95% CI, 0.70‐0.95), while the between‐day SD was 0.50 (95% CI, 0.43‐0.60).ConclusionsThere is interlot variability in the tested HLA detection assay as well as significant bias between lots. It may be reasonable to develop a new cutoff when a new lot is obtained.