Jacobs, Jeremy W.

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.

Abstract Objectives Fluorescence resonance energy transfer (FRET)–based ADAMTS13 activity assays are critical for the diagnosis of thrombotic thrombocytopenic purpura. However, these assays are susceptible to interference. As iodide has been suggested to interfere in laboratory testing via fluorophore quenching or promotion, we aimed to determine whether iodinated contrast (Omnipaque) interferes with the ATS-13 ADAMTS13 Activity Assay 2.0. Methods We evaluated the excitation, emission, and absorbance spectrum of Omnipaque alone and spiked in patient plasma with known ADAMTS13 activity and ADAMTS13 activity on Omnipaque alone, an abnormal control of patient plasma previously observed to display elevated baseline relative fluorescent units, and variable concentrations of patient plasma with known ADAMTS13 activity spiked with Omnipaque. Results No atypical fluorescent peaks were observed on any sample (Omnipaque alone or spiked in plasma) between 250 and 700 nm. There was no difference in the mean ADAMTS13 activity among the various concentrations of plasma spiked with Omnipaque or plasma spiked with saline. Conclusions Iodinated contrast does not appear to interfere—either via spectral overlap of the fluorophore or through physiologic inhibition of the ADAMTS13 enzyme—with ADAMTS13 activity FRET-based assays based on the findings from this in vitro analysis. Delaying sample collection for ADAMTS13 activity testing from suspected patients with thrombotic thrombocytopenic purpura following administration of iodinated radiocontrast agents is not necessary, and recent contrast administration should not yield erroneous ADAMTS13 activity results.

AbstractBackgroundHemolytic disease of the fetus and newborn (HDFN) is caused by maternal alloantibody‐mediated destruction of fetal/neonatal red blood cells (RBCs). While the pathophysiology has been well‐characterized, the clinical and laboratory monitoring practices are inconsistent.MethodsWe surveyed 103 US institutions to characterize laboratory testing practices for individuals with fetuses at risk of HDFN. Questions included antibody testing and titration methodologies, the use of critical titers, paternal and cell‐free fetal DNA testing, and result reporting and documentation practices.ResultsThe response rate was 44% (45/103). Most respondents (96%, 43/45) assess maternal antibody titers, primarily using conventional tube‐based methods only (79%, 34/43). Among respondents, 51% (23/45) rescreen all individuals for antibodies in the third trimester, and 60% (27/45) perform paternal RBC antigen testing. A minority (27%, 12/45) utilize cell‐free fetal DNA (cffDNA) testing to predict fetal antigen status. Maternal antibody titers are performed even when the fetus is not considered to be at risk of HDFN based on cffDNA or paternal RBC antigen testing at 23% (10/43) of sites that assess titers.DiscussionThere is heterogeneity across US institutions regarding the testing, monitoring, and reporting practices for pregnant individuals with fetuses at risk of HDFN, including the use of antibody titers in screening and monitoring programs, the use of paternal RBC antigen testing and cffDNA, and documentation of fetal antigen results. Standardization of laboratory testing protocols and closer collaboration between the blood bank and transfusion medicine service and the obstetric/maternal‐fetal medicine service are needed.

AbstractBackgroundTrauma remains the leading cause of pediatric mortality in the United States. Although use of massive transfusion protocols (MTPs) in this population is widespread, optimal pediatric resuscitation is not well established. We sought to assess contemporary pediatric MTP practice in the United States.Study Design and MethodsA web‐based survey was designed by the Association for the Advancement of Blood & Biotherapies (AABB) Pediatric Transfusion Medicine Subsection and distributed to select American College of Surgeons (ACS) Level I Verified pediatric trauma centers. The survey assessed current MTP policy, implementation, and recent changes in practice.ResultsResponse rate was 55% (22/40). Almost half of the respondents were from the South. The median RBC:plasma ratio was 1 (interquartile range 1–1.5). Protocolized fibrinogen supplementation was common while integration of antifibrinolytic therapy into MTPs was infrequent. Viscoelastic testing (VET) was available at most sites, 71% (15/21, one site did not respond), and was generally utilized on an ad‐hoc basis. Roughly, a third of sites had changed their MTP in the past 3 years due to blood supply issues, and about a third reported having group O Whole Blood on‐site.ConclusionMTP practice is similar throughout the United States. Though fibrinogen supplementation is common—other emerging interventions such as antifibrinolytic therapy or utilization of routine viscoelastic testing—are not widespread. Pediatric transfusion medicine experts must continue to follow practice change, as contemporary large trials begin to characterize new supportive modalities to optimize resuscitation in pediatric trauma patients.

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.

AbstractIntroductionApheresis practices in the United States (US) have not been comprehensively characterized to date. This study aimed to address this gap by evaluating apheresis therapy through a national survey.MethodsA multi‐institutional survey was conducted between April and July 2023. The survey, comprising 54 questions, focused on institutional demographics, procedures, equipment, staffing, training, and impacts of the Coronavirus Disease 2019 (COVID‐19) pandemic. Responses from 22 institutions, primarily academic medical centers, were analyzed.ResultsTherapeutic plasma exchange (TPE) was the most common procedure, followed by hematopoietic progenitor cell collection (HPC‐A) and red blood cell exchange (RCE). CAR‐T cell collections were widespread, with some institutions supporting over 30 protocols concurrently. Most sites used the Spectra Optia Apheresis System, were managed by a transfusion medicine service, and employed internal apheresis providers. Insufficient staffing levels, exacerbated by the COVID‐19 pandemic, were common and most often addressed using overtime.DiscussionThe survey highlighted the ubiquity of TPE, expanding cellular collections and staffing challenges. The role of apheresis in supporting cellular therapy, particularly in newly developing cell and gene therapies and clinical trials, was evident. Staffing issues during the pandemic emphasized the need for innovative recruitment strategies.ConclusionThis nationwide survey provides the most comprehensive analysis to date of apheresis practices in large US academic centers.

Background and Objectives: Clinical practice guidelines (CPGs) have significantly influenced medical practice worldwide. Nevertheless, the authorship of CPGs produced by several medical societies has not been representative of the field and population they address, as women and individuals from racial and ethnic minority groups have been underrepresented as authors. We hypothesized that women and individuals from minoritized racial and ethnic groups would also be underrepresented as authors of CPGs produced by the American Academy of Pediatrics (AAP). Methods: In this cross-sectional study, the gender, race, and ethnic composition of authors and subcommittee participants of AAP-produced CPGs published from January 2010 through May 2023 were analyzed and compared to the 2010 and 2021 U.S. population and 2010 and 2022 U.S. medical school pediatric faculty. Results: Women (39.7%, 127/320 of all positions, and 42.5%, 85/200 of named author positions) and women physicians (35.2%, 101/287 of all positions, and 36.4%, 64/176 of named author positions) were significantly underrepresented—while men and men physicians were significantly overrepresented—from their respective composition in the U.S. Census and pediatric faculty. Women and women physicians from all racial and ethnic groups and men and men physicians from minority racial and ethnic groups were significantly underrepresented—from their respective composition in the U.S. Census and pediatric faculty. No Black man was identified as an author. Conclusions: Medical societies that produce CPGs should be cognizant of these inequities and ensure appropriate authorship diversity.