Stowell, Sean R.

Abstract Background Red cell alloimmunization complicates sickle cell disease (SCD) management despite current widespread prophylactic Rh/K matching in the United States (US). Regional antibody patterns remain poorly characterized. Study Design and Methods We conducted a retrospective analysis of 2965 SCD patients from 9 US sites (2010–2022). All hospitals prophylactically match for Rh and K antigens. Each site collected demographics, antigen status, antibody histories, and antibody screen results from their laboratory information system. Results Overall antibody prevalence was 29.7% with dramatic institutional variation (17.9%–56.0%). Alloantibody prevalence was 27.5%. Most autoantibody‐positive patients (74.23%) also had alloantibodies, identifying a high‐risk population. A third of patients with positive antibody histories had negative screens. Pediatric patients showed markedly different antibody profiles than adults. Hospitals’ antibody patterns clustered by patient age rather than geography. Rh and K antibodies were the most common and also most likely to co‐occur, followed by S, Fya, and Jkb antibodies. Antibodies against Jsa (1.82%), V (1.75%), and Kpa (1.69%) were more prevalent than anti‐Jka (1.28%). Despite regional antibody variation, antigen frequencies remained overall consistent. In antigen–antibody pairwise comparisons, 3.15% were antigen‐negative and antibody‐positive reflecting alloimmunization; 0.47% were both antibody‐ and antigen‐positive, suggesting partial/variant antigens. Discussion Substantial institutional variation in antibody prevalence suggests need for site‐specific approaches to testing and prophylactic matching. High co‐occurrence of auto‐ and alloantibodies, antibody immunogenicity patterns, and antigen–antibody discordances support the need for further research and consideration of refined testing and/or matching strategies beyond the current Rh and K standard.

ABSTRACT A major challenge in hematopoietic progenitor cell apheresis is determining the whole blood (WB) volume to process to achieve a CD34+ cell collection goal. We developed a web‐based calculator app that uses the Collection Efficiency 2 (CE2) model to estimate personalized WB processing volumes needed to reach a prescribed CD34+ cell collection goal. Retrospective evaluation of the app using collection data from two academic medical centers showed that actual processed WB volumes were frequently higher than the app's recommendations. The frequency of potential under‐collection events is predicted to be low had the app‐calculated volumes been utilized. Our findings suggest that using the app's recommendations may lower total WB processing volumes, reducing over‐collection and time spent on the apheresis machine, while maintaining a low under‐collection risk profile.

AbstractBackgroundImmune thrombotic thrombocytopenic purpura (iTTP) is a hematologic disorder characterized by severe acquired deficiency in ADAMTS13, resulting in thrombotic microangiopathy and death if untreated. Plasma exchange (PLEX) is the backbone of iTTP management and has improved survival in this disorder. Guidelines suggest initiation of PLEX within 4–8 h of presentation; however, there is little evidence to guide the precise timing of PLEX, and barriers exist to its timely deployment.Study design and methodsWe examined determinants of time between symptom onset to PLEX initiation (S2P) and hospital presentation to PLEX initiation (door to PLEX, D2P) in a large iTTP research cohort at an academic medical center.ResultsIn 225 cases occurring in 143 unique patients, the median (IQR) S2P time was 4.28 (1.92–7.47) days. In linear mixed effects regression analysis, increased S2P was associated with greater distance from a participating apheresis center (p = .01) and higher presenting platelet count (p = .046), while relapse presentation was associated with shorter S2P (p = .036). The median (IQR) D2P time was 8.4 (5.03–15.63) h. Longer D2P time was associated with a higher presenting platelet count (p = .002) and trended towards association with male sex (p = .057). Increased S2P and D2P times were not associated with hospital length of stay, mortality, or the composite of mortality and ICU stay.ConclusionOur data show that different factors contribute to the interval between symptom onset and presentation versus the time between presentation and initiation of therapy in iTTP.

Abstract In July 2022, these guidelines were reviewed by an expert work group convened by ASH. Review included limited searches for new evidence and discussion of the search results. Following this review, the ASH Committee on Quality agreed to continue monitoring the supporting evidence rather than revise or retire these guidelines at this time. Limited searches and expert review will be repeated annually going forward until these guidelines are revised or retired. Background: Red cell transfusions remain a mainstay of therapy for patients with sickle cell disease (SCD), but pose significant clinical challenges. Guidance for specific indications and administration of transfusion, as well as screening, prevention, and management of alloimmunization, delayed hemolytic transfusion reactions (DHTRs), and iron overload may improve outcomes. Objective: Our objective was to develop evidence-based guidelines to support patients, clinicians, and other healthcare professionals in their decisions about transfusion support for SCD and the management of transfusion-related complications. Methods: The American Society of Hematology formed a multidisciplinary panel that was balanced to minimize bias from conflicts of interest and that included a patient representative. The panel prioritized clinical questions and outcomes. The Mayo Clinic Evidence-Based Practice Research Program supported the guideline development process. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to form recommendations, which were subject to public comment. Results: The panel developed 10 recommendations focused on red cell antigen typing and matching, indications, and mode of administration (simple vs red cell exchange), as well as screening, prevention, and management of alloimmunization, DHTRs, and iron overload. Conclusions: The majority of panel recommendations were conditional due to the paucity of direct, high-certainty evidence for outcomes of interest. Research priorities were identified, including prospective studies to understand the role of serologic vs genotypic red cell matching, the mechanism of HTRs resulting from specific alloantigens to inform therapy, the role and timing of regular transfusions during pregnancy for women, and the optimal treatment of transfusional iron overload in SCD.