Wu, Yanyun

ABSTRACT Prior surveys of chronic automated red blood cell exchange (RCE) for patients with sickle cell disease (SCD) have identified considerable procedural variability, especially with the use of isovolemic hemodilution red blood cell exchange (IHD‐RCE). We conducted a survey of chronic RCE practices among American Society for Apheresis (ASFA) members to identify opportunities for practice harmonization and future studies. The ASFA SCD Research Subcommittee developed a 72‐item survey of chronic RCE practices, with a focus on IHD‐RCE. The survey was validated internally and distributed by email to all ASFA members from September 2024 to February 2025. One survey response from each institution was retained for data analysis. Descriptive statistics were performed. Sixty‐two survey responses, including three from international institutions, were retained for analysis. Sixty‐one percent of respondents (38/62) reported using at least one fixed RCE target, with end hematocrit being the most common fixed parameter (40%, 25/62), followed by fraction of cells remaining (31%, 19/62) and hemoglobin S% (27%, 17/62). Most respondents (60%, 37/61) performed IHD‐RCE at their institution, though other details such as the minimum hematocrit, exclusion criteria, and response to adverse effects were variable. Consistent pre‐ and post‐RCE laboratory monitoring practices were reported. Consistent with earlier surveys, procedural variability in chronic RCE practices for patients with SCD is observed. This highlights opportunities to compare outcomes where practice variability exists. Consensus guidelines based on institutional practices with optimal outcomes should be developed.

Abstract Background Sickle cell disease (SCD) is a hemoglobinopathy with limited treatment options. Genetic modification of the patient's own hematopoietic stem cells (HSCs) offers an avenue to curative therapy using the patient's own cells. Many challenges exist in collecting sufficient numbers of starting material for manufacturing, beginning with the pre‐mobilization optimization of the patient to the mobilization, collection, and post‐collection phases. Study Design and Methods A working group within the Cellular Therapy Subcommittee of the American Society for Apheresis Clinical Applications Committee describes the challenges associated with apheresis collection of the starting material for gene therapy (GT) product manufacturing for patients with SCD and discusses potential strategies for overcoming these challenges. Results and Discussion Patients must undergo automated red blood cell exchange (RCE) to lower hemoglobin S in a relatively short window of time before apheresis collection of HSCs. The risks and benefits of transfusion as well as the logistics of providing adequate and appropriate blood products must be considered. Limited agents are available for mobilization of HSCs into the peripheral blood for collection and the timing of administration is short. Each collection cycle consists of RCE followed by at least three mobilization and apheresis collection events in addition to collecting backup cells. More than one cycle is typically needed to collect enough cells for GT drug product manufacturing. Optimization of patient factors and apheresis instrument parameters leads to better collection yields. Early and frequent ongoing coordination with all stakeholders involved is critical to developing personalized treatment plans for patients.

ABSTRACTImmune thrombotic thrombocytopenic purpura (iTTP) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular occlusion secondary to acquired ADAMTS13 deficiency. Contemporary data regarding iTTP treatment practices in the US, including the use of caplacizumab, are lacking. We aimed to characterize the demographics and therapies, including medications and apheresis practices, in patients with iTTP in the US. We retrospectively analyzed iTTP cases at 15 sites in the US that provide comprehensive care for patients with iTTP. The time‐period assessed was from January 1, 2017 to December 31, 2021. Our primary objective was to analyze data by iTTP episode, inclusive of initial episodes and relapses. A total of 390 iTTP episodes were reported for 280 unique individuals (187 females, 93 males). Thirty‐day mortality was 3.7% (14/374), and 6‐month mortality was 7.4% (27/367). TPE details were reported for 343 episodes, among which 261 underwent at least one procedure (median 6, IQR 3–11). Among the 261 episodes with at least one therapeutic plasma exchange (TPE) performed, 82.0% (214/261) used only plasma. Caplacizumab was used either alone or in combination with other agents in 43 (11.0%) episodes. Management strategies for iTTP remain varied across centers in the US, with a variety of combinations for TPE replacement fluids and therapeutic agents, as well as limited use of caplacizumab. Further research and standardization of treatment regimens may further reduce mortality in this condition.

ABSTRACTApheresis is performed worldwide for an increasing number of indications. The development of common data elements (CDE) for apheresis related areas may facilitate conduct of new research, enhance quality initiatives including benchmarking, and improve patient care. This report describes the systematic development of the Uniform Apheresis Case Report Form (UACRF) as part of the Apheresis in the United States (ApheresUS) program. A consensus panel of 17 diverse experts in apheresis, related specialties, and electronic case report form (eCRF), and database development was assembled. The panel met via online conferencing from November 17, 2020 to December 1, 2021. A draft document was posted online for public comment from October 11, 2021 to November 10, 2021. Feedback was collected using an online survey tool. The consensus panel revised the UACRF. This version was converted to an eCRF with additional changes made to improve usability in this format. The final version of the UACRF was created on August 24, 2023. The UACRF contains 16 modules: procedure and subject eligibility, patient demographics, general procedure information, laboratory parameters, vascular access, common procedure elements, eight procedure specific modules (mononuclear cell collection and seven therapeutic modalities), outcomes, and site information. A total of 137 data elements were created, including 57 with one or more subelements. The UACRF is the first systematic attempt to develop CDE for therapeutic apheresis and white blood cell collections. Further validation of the UACRF is necessary to confirm the tool's ability to collect the relevant data elements and determine the usability of the form.

AbstractPrior studies have suggested that immune thrombotic thrombocytopenic purpura (iTTP) may display seasonal variation; however, methodologic limitations and sample sizes have diminished the ability to perform a rigorous assessment. This 5‐year retrospective study assessed the epidemiology of iTTP and determined whether it displays a seasonal pattern. Patients with both initial and relapsed iTTP (defined as a disintegrin and metalloprotease with thrombospondin type motifs 13 activity <10%) from 24 tertiary centers in Australia, Canada, France, Greece, Italy, Spain, and the US were included. Seasons were defined as: Northern Hemisphere—winter (December–February); spring (March–May); summer (June–August); autumn (September–November) and Southern Hemisphere—winter (June–August); spring (September–November); summer (December–February); autumn (March–May). Additional outcomes included the mean temperature in months with and without an iTTP episode at each site. A total of 583 patients experienced 719 iTTP episodes. The observed proportion of iTTP episodes during the winter was significantly greater than expected if equally distributed across seasons (28.5%, 205/719, 25.3%–31.9%; p = .03). Distance from the equator and mean temperature deviation both positively correlated with the proportion of iTTP episodes during winter. Acute iTTP episodes were associated with the winter season and colder temperatures, with a second peak during summer. Occurrence during winter was most pronounced at sites further from the equator and/or with greater annual temperature deviations. Understanding the etiologies underlying seasonal patterns of disease may assist in discovery and development of future preventative therapies and inform models for resource utilization.

Context.— The blood bank is often consulted for transfusion support of patients with suspected platelet transfusion refractoriness (PTR). The workup is complex because testing includes specialized assays that are uncommonly ordered with limited availability. Add to this the variety of possible products—crossmatched platelets, human leukocyte antigen (HLA)–matched platelets, HLA antigen–negative platelets—and the approach to PTR can be overwhelming. Moreover, most literature on the subject is published in transfusion medicine journals aimed at transfusion medicine physicians and blood bank specialists in academic settings. Resources tailored to community hospital blood banks are lacking. Objective.— To provide pathologists who may not have subspecialized training in transfusion medicine and who direct blood bank algorithmic workflows based on clinical scenario and test availability to provide appropriate transfusion support for patients with PTR. Data Sources.— This review is a comprehensive overview of terminology, HLA testing procedures, interpretations, and practical recommendations for managing PTR in various scenarios based on expert opinion as well as relevant medical literature published from 2007 to 2022. Conclusions.— Consultation on PTR is complicated and encompasses many clinical and laboratory aspects. The lack of guidelines derived from high-quality prospective studies poses challenges in the workup and management of PTR. Hindering the process further are limited test availability, unfamiliarity with the technical assays, and the various specialized platelet products. The clinical evaluation algorithm presented herein along with the workflow pathways offer pathologists user-friendly and best-practice guidelines with different options based on the clinical scenario and the tests available.

AbstractSince 1986, the American Society for Apheresis (ASFA) has published practice guidelines on the use of therapeutic apheresis in the Journal of Clinical Apheresis (JCA) Special Issue. Since 2007, updated guidelines have been published every 3 years to reflect current evidence based apheresis practice with the most recent edition (8th) published in 2019. With each edition, the guidelines are reviewed and updated based on any newly published literature since the last review. The PEXIVAS study, an international, randomized controlled trial comparing therapeutic plasma exchange (TPE) vs no TPE and standard vs reduced dose steroid regimen on the primary composite outcome of end stage renal disease or death in patients with ANCA‐associated vasculitis (AAV), was published in February 2020. This study represents the largest study on the role of therapeutic apheresis in AAV published to date and prompted the JCA Special Issue Writing Committee to reassess the current AAV fact sheet for updates based on this newly available evidence. This interim fact sheet summarizes current ASFA recommendations for the evidence‐based use of therapeutic apheresis in AAV and supersedes the recommendations published in the 2019 guidelines.

AbstractImportanceNeuromyelitis optica/neuromyelitis optica spectrum disorder patients' response to therapeutic plasma exchange (TPE) is currently incompletely characterized.ObjectiveOur study aims to understand the clinical status improvement of neuromyelitis optica/neuromyelitis optica spectrum disorder patients treated with TPE.Design, Setting, and ParticipantsThis is a multicenter retrospective study conducted between 1 January 2003 and 31 July 2017 at 13 US hospitals performing apheresis procedures. Subjects studied were diagnosed with neuromyelitis optica/neuromyelitis optica spectrum disorder who received TPE during presentation with acute disease.Main Outcomes and MeasuresThe primary outcome was clinical status improvement in patients treated with TPE. Secondary measures were procedural and patient characteristics associated with response to treatment.ResultsWe evaluated 114 patients from 13 institutions. There was a female predilection. The largest ethnic group affected was non‐Hispanic Caucasian. The average age of diagnosis was 43.1 years. The average time to diagnosis was 3.1 years. On average, five procedures were performed during each treatment series. The most commonly performed plasma volume exchange was 1.0 to 1.25 using 5% albumin as replacement fluid. Most patients (52%) did not require an additional course of TPE and noted “mild” to “moderate” clinical status improvement. Maximal symptom improvement appeared by the fourth or fifth TPE treatment.Conclusion and RelevanceTPE improved the clinical status of patients. Adults responded more favorably than children. Procedural characteristics, including number of TPEs, plasma volume exchanged, and replacement fluid used, were similar between institutions. TPE was well‐tolerated and had a low severe adverse event profile.

Abstract Background: Use of direct-acting oral anticoagulants (DOAC) is increasingly common among patients with atrial fibrillation and venous thromboembolic disease. Differences in the mechanisms of action as compared to warfarin could impact transfusion patterns and clinical outcomes in patients, especially for those presenting with major hemorrhage. The management of patients taking these newer medications and corresponding outcomes are relevant to optimizing clinical decision making in situations of major hemorrhage. Methods: We tested the hypothesis that inpatient all-cause mortality among patients presenting with major hemorrhage differs based on the home-administered anticoagulant medication class (DOAC versus warfarin). A cohort of patients presenting to twelve US hospitals from 2013 to 2016 was identified using the Recipient Epidemiology and Donor Evaluation Study (REDS)-III Recipient Database. Primary ICD diagnosis codes, issued blood products, laboratory data, and early mortality events were used in the application of the International Society on Thrombosis and Hemostasis definition of major hemorrhage. Exposure status was defined as a record of home-administered DOAC (apixaban, dabigatran, edoxaban, or rivaroxaban; exposed) or warfarin (non-exposed). Patients with multiple encounters and those transferred into or out of network were excluded from the analysis. Proportional hazards regression was used to compare all-cause mortality and hospital length of stay. We then repeated the analysis using a cohort matched on propensity scores to account for confounding by age, gender, concurrent aspirin and anti-platelet use, liver and renal dysfunction, cancer, CHA2DS2-VASc score, traumatic injury, and hospital. We then repeated the propensity score matched analysis stratified by anatomic location of bleed and traumatic injury. Results: More than 1.5 million hospitalizations were screened for eligibility. Exclusion of minors, outpatients, hospitalizations without a medication of interest, absence of major hemorrhage, multiple hospitalizations, and hospital transfers resulted in 3,731 patients available for the unadjusted analysis. Inpatient all-cause mortality was lower among DOAC users when the entire cohort was considered (HR = 0.60, 95%CI 0.45 - 0.80, p=0.0005). Implementation of propensity score matching to account for confounding abrogated this difference (HR=0.84, 95%CI 0.58 - 1.22, p=0.36). Time to hospital discharge was shorter for DOAC users (HR = 1.17, 95%CI 1.05 - 1.30, p=0.0034). Transfusion patterns were similar by medication, except for plasma transfusion occurring in 42% of warfarin encounters and 11% of DOAC encounters. Vitamin K was administered in 63% of warfarin encounters, whereas specific DOAC reversal agents were largely unavailable during the analysis period [used in 5 (1%) DOAC encounters]. There were no statistically significant differences in inpatient all-cause mortality in the stratified analysis (warfarin as reference): HR = 0.69 (95%CI 0.31 - 1.55) for traumatic head injuries; HR = 1.10 (95%CI 0.62 - 1.95) for non-traumatic head injuries; HR = 0.62 (95%CI 0.20 - 1.94) for traumatic, non-head injuries; and HR = 0.69 (95%CI 0.29 - 1.63) for non-traumatic, non-head injuries. Conclusions: Analysis of a population taking oral anticoagulation and presenting with major hemorrhage showed that transfusion of plasma was more commonly employed to treat major hemorrhage among warfarin users than DOAC users. Inpatient all-cause mortality was lower among DOAC users in the overall cohort; however, accounting for potential confounding factors using propensity score matching abrogated this difference. Hospital length of stay was shorter for DOAC users compared to warfarin users. Stratification by location of bleed and traumatic injury did not alter these findings. Less plasma use and a shorter length of hospitalization in this study, combined with no observable difference in inpatient all-cause mortality, suggests that outcomes following major hemorrhage are at least no different for DOAC users as compared to warfarin users. Disclosures Mast: Novo Nordisk: Research Funding. Kor:NIH: Consultancy; NIH: Research Funding; UpToDate: Patents & Royalties; CSL Behring: Honoraria.