Grossman, Brenda J.

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.

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.

Abstract Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immunocompromised (IC) patients. IC patients have a higher risk of persistent infection, severe disease, and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has yet to be determined, and related best practices guidelines are lacking. A group of individuals with expertise spanning infectious diseases, virology and transfusion medicine was assembled to render an expert opinion statement pertaining to the use of CCP for IC patients. For optimal effect, CCP should be recently and locally collected to match circulating variant. CCP should be considered for the treatment of IC patients with acute and protracted COVID-19; dosage depends on clinical setting (acute vs protracted COVID-19). CCP containing high-titer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, retains activity against circulating SARS-CoV-2 variants, which have otherwise rendered monoclonal antibodies ineffective.

Background and ObjectivesABO blood group may affect risk of SARS‐CoV‐2 infection and/or severity of COVID‐19. We sought to determine whether IgG, IgA and neutralizing antibody (nAb) to SARS‐CoV‐2 vary by ABO blood group.Materials and MethodsAmong eligible convalescent plasma donors, ABO blood group was determined via agglutination of reagent A1 and B cells, IgA and IgG were quantified using the Euroimmun anti‐SARS‐CoV‐2 ELISA, and nAb titres were quantified using a microneutralization assay. Differences in titre distribution were examined by ABO blood group using non‐parametric Kruskal–Wallis tests. Adjusted prevalence ratios (aPR) of high nAb titre (≥1:160) were estimated by blood group using multivariable modified Poisson regression models that adjusted for age, sex, hospitalization status and time since SARS‐CoV‐2 diagnosis.ResultsOf the 202 potential donors, 65 (32%) were blood group A, 39 (19%) were group B, 13 (6%) were group AB, and 85 (42%) were group O. Distribution of nAb titres significantly differed by ABO blood group, whereas there were no significant differences in anti‐spike IgA or anti‐spike IgG titres by ABO blood group. There were significantly more individuals with high nAb titre (≥1:160) among those with blood group B, compared with group O (aPR = 1·9 [95%CI = 1·1–3·3], P = 0·029). Fewer individuals had a high nAb titre among those with blood group A, compared with group B (aPR = 0·6 [95%CI = 0·4‐1·0], P = 0·053).ConclusionEligible CCP donors with blood group B may have relatively higher neutralizing antibody titres. Additional studies evaluating ABO blood groups and antibody titres that incorporate COVID‐19 severity are needed.

AbstractBackgroundAlthough many apheresis centers offer extracorporeal photopheresis (ECP), little is known about current treatment practices.MethodsAn electronic survey was distributed to assess ECP practice internationally.ResultsOf 251 responses, 137 met criteria for analysis. Most respondents were from North America (80%). Nurses perform ECP at most centers (84%) and the majority of centers treat adults only (52%). Most centers treat fewer than 50 patients/year (83%) and perform fewer than 300 procedures/year (70%). Closed system devices (XTS and/or Cellex) are used to perform ECP at most centers (96%). The most common indications for ECP are acute/chronic skin graft versus host disease (89%) and cutaneous T‐cell lymphoma (63%). The typical wait time for ECP treatment is less than 2 weeks (91%). Most centers do not routinely perform quality control assessment of the collected product (66%). There are device‐specific differences in treatment parameters. For example, XTS users more frequently have a minimum weight limit (P = 0.003) and use laboratory parameters to determine eligibility for treatment (P = 0.03). Regardless of device used, the majority of centers assess the clinical status of the patient before each procedure. Greater than 50% of respondents would defer treatment for hemodynamic instability due to active sepsis or heart failure, positive blood culture in the past 24 h or current fever.ConclusionThis survey based study describes current ECP practices. Further research to provide evidence for optimal standardization of patient qualifications, procedure parameters and product quality assessment is recommended.

BACKGROUNDLeukoreduced (LR) or cytomegalovirus (CMV)‐seronegative cellular blood components are commonly used to reduce the risk of transfusion‐transmitted CMV infection in high‐risk patients.STUDY DESIGN AND METHODSWe performed a systematic review and meta‐analysis to evaluate the evidence for the use of LR cellular blood components with or without concurrent CMV testing of donor units in patients undergoing chemotherapy or solid organ and hematopoietic stem cell transplantation, in pregnant women, in very‐low‐birthweight infants, and in patients with primary immunodeficiency. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from 1980 through February 2015. Studies were included if they had a comparison group. Two independent reviewers selected and appraised studies. Meta‐analysis was performed when appropriate.RESULTSOf 457 studies screened, 11 were eligible. One study was excluded from the meta‐analysis because the comparison performed differed significantly from the others. Meta‐analysis of five studies that compared leukoreduction to transfusing CMV‐untested blood components showed no significant difference in clinical CMV infection (relative risk [RR], 0.26; 95% confidence interval [CI], 0.04‐1.57) or laboratory CMV infection (RR, 0.33; 95% CI, 0.08‐1.37). Meta‐analysis of three studies that compared leukoreduction to transfusing CMV‐seronegative cellular components showed no significant difference in laboratory CMV infection (RR, 2.18; 95% CI, 0.96‐4.98). Meta‐analysis of two studies that compared adding CMV testing to leukoreduction (vs. leukoreduction alone) showed no significant difference in clinical or laboratory CMV infection. The certainty in estimates was low for all comparisons.CONCLUSIONAt present, the scientific evidence does not favor a single strategy for reducing the risk of transfusion‐related CMV infection in high‐risk patients.