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The virtual crossmatch (VXM) has become a critical tool to predict the compatibility between an organ donor and a potential recipient. Yet, nonstandardized laboratory practice can lead to variability in VXM interpretation. Therefore, UCLAs VXM Exchange survey was designed to understand factors that influence the variability of VXM prediction in the presence of HLA donor-specific antibody (DSA). Thirty-six donor blood samples and 72 HLA reference sera were sent to 35 participating laboratories to perform HLA antibody testing, flow crossmatch (FXM), and VXM from 2014 to 2019, consisting of 144 T/B-cell FXM pairs and 112 T/B-cell VXM pairs. In the FXM survey, 86% T-cell FXM and 84% B-cell FXM achieved >80% concordance among laboratories. In the VXM survey, 81% T-cell VXM and 80% VXM achieved >80% concordance. The concordance between FXM and VXM was 79% for T cell and 87% for B cell. The consensus between VXM and FXM was high with strong DSA. However, significant variability was observed in sera with (1) very high titer antibodies that exit prozone effect; (2) weak-to-moderate DSA, particularly in the presence of multiple weak DSAs; and (3) DSA against lowly expressed antigens. With the increasing use the VXM, standardization and continuous learning via exchange surveys will provide better understanding and quality controls for VXM to improve accuracy across all centers.

BackgroundDespite the institution of a new Kidney Allocation System in 2014, A2/A2B to B transplantation has not increased as expected. The current Organ Procurement and Transplantation Network policy requires subtyping on two separate occasions, and in the setting of discrepant results, defaulting to the A1 subtype. However, there is significant inherent variability in the serologic assays used for blood group subtyping and genotyping is rarely done.MethodsThe National Kidney Registry, a kidney paired donation (KPD) program, performs serological typing on all A/AB donors, and in cases of non-A1/non-A1B donors, confirmatory genotyping is performed.ResultsBetween 2/18/2018 and 9/15/2020, 13.0% (145) of 1,111 type A donors registered with the NKR were ultimately subtyped as A2 via genotyping. Notably, 49.6% (72) of these were subtyped as A1 at their donor center, and in accordance with OPTN policy, ineligible for allocation as A2.ConclusionInaccurate A2 subtyping represents a significant lost opportunity in transplantation, especially in KPD where A2 donors can not only facilitate living donor transplantation for O and highly sensitized candidates, but can also facilitate additional living donor transplants. This study highlights the need for improved accuracy of subtyping technique, and the need for policy changes encouraging optimal utilization of A2 donor kidneys.

ObjectivesTo determine if transfusing ABO compatible platelets has a greater effect on incremental change in platelet count as compared to ABO incompatible platelets in critically ill children.DesignSecondary analysis of a prospective, observational study. Transfusions were classified as either ABO compatible, major incompatibility, or minor incompatibility. The primary outcome was the incremental change in platelet count. Transfusion reactions were analyzed as a secondary outcome.SettingEighty-two PICUs in 16 countries.PatientsChildren (3 d to 16 yr old) were enrolled if they received a platelet transfusion during one of the predefined screening weeks.InterventionsNone.Measurements and main resultsFive-hundred three children were enrolled and had complete ABO information for both donor and recipient, as well as laboratory data. Three-hundred forty-two (68%) received ABO-identical platelets, 133 (26%) received platelets with major incompatibility, and 28 (6%) received platelets with minor incompatibility. Age, weight, proportion with mechanical ventilation or underlying oncologic diagnosis did not differ between the groups. After adjustment for transfusion dose, there was no difference in the incremental change in platelet count between the groups; the median (interquartile range) change for ABO-identical transfusions was 28 × 10 cells/L (8-68 × 10 cells/L), for transfusions with major incompatibility 26 × 10 cells/L (7-74 × 10 cells/L), and for transfusions with minor incompatibility 54 × 10 cells/L (14-81 × 10 cells/L) (p = 0.37). No differences in count increment between the groups were noted for bleeding (p = 0.92) and nonbleeding patients (p = 0.29). There were also no differences observed between the groups for any transfusion reaction (p = 0.07).ConclusionsNo differences were seen in the incremental change in platelet count nor in transfusion reactions when comparing major ABO incompatible platelet transfusions with ABO compatible transfusions in a large study of critically ill children. Studies in larger, prospectively enrolled cohorts should be performed to validate whether ABO matching for platelet transfusions in critically ill children is necessary.

One criticism of kidney paired donation (KPD) is that easy-to-match candidates leave the registry quickly, thus concentrating the pool with hard-to-match sensitized and blood type O candidates. We studied candidate/donor pairs who registered with the National Kidney Registry (NKR), the largest US KPD clearinghouse, from January 2012-June 2016. There were no changes in age, gender, BMI, race, ABO blood type, or panel-reactive antibody (PRA) of newly registering candidates over time, with consistent registration of hard-to-match candidates (59% type O and 38% PRA ≥97%). However, there was no accumulation of type O candidates over time, presumably due to increasing numbers of nondirected type O donors. Although there was an initial accumulation of candidates with PRA ≥97% (from 33% of the pool in 2012% to 43% in 2014, P = .03), the proportion decreased to 17% by June 2016 (P

One criticism of kidney paired donation (KPD) is that easy-to-match candidates leave the registry quickly, thus concentrating the pool with hard-to-match sensitized and blood type O candidates. We studied candidate/donor pairs who registered with the National Kidney Registry (NKR), the largest US KPD clearinghouse, from January 2012-June 2016. There were no changes in age, gender, BMI, race, ABO blood type, or panel-reactive antibody (PRA) of newly registering candidates over time, with consistent registration of hard-to-match candidates (59% type O and 38% PRA ≥97%). However, there was no accumulation of type O candidates over time, presumably due to increasing numbers of nondirected type O donors. Although there was an initial accumulation of candidates with PRA ≥97% (from 33% of the pool in 2012% to 43% in 2014, P = .03), the proportion decreased to 17% by June 2016 (P

Daratumumab has proven to be highly efficacious for relapsed and refractory multiple myeloma (MM) and has recently been approved in the frontline setting for MM patients ineligible for transplantation. In the future, expanded indications are possible for daratumumab and other anti-CD38 monoclonal antibodies in development. For several years, it has been recognized that these therapies interfere with blood bank testing by binding to CD38 on red blood cells and causing panagglutination on the Indirect Antiglobulin Test. This can lead to redundant testing and significant delays in patient care. Given the anticipated increase in utilization of anti-CD38 monoclonal antibodies, as well as the transfusion needs of MM patients, it is critical to understand the nature of this interference with blood bank testing and to optimize clinical and laboratory procedures. In this review, we summarize the pathophysiology of this phenomenon, examine the clinical data reported to date, describe currently available methods to resolve this issue, and lastly provide a guide to clinical management of blood transfusions for patients receiving anti-CD38 monoclonal antibodies.

Deceased donor kidney allocation was reorganized in the United States to address several problems, including the highly sensitized patients disadvantaged with large, diverse repertoires of antibodies. Here, five transplant surgeons review their center's experience with the new allocation changes: highlighting areas of accomplishment, opportunities for improvement and, in some cases, stark differences in practice. Across these five centers the highly sensitized patients (CPRA ⩾98%) range from 5.5 to 9.2% of the 12,364 candidates on their collective waitlist. All centers reported greater rates of kidney transplantations in highly sensitized patients (12.4-27%). Three of the programs (Emory, UCSF, UW) relied upon the virtual crossmatch prior to organ acceptance in a majority of cases (70-86%)-the mere presence of antibody on HLA antibody screen was sufficient to exclude the donor in most cases at Emory and UCSF. Penn and UAB relied upon the physical flow crossmatch in almost all cases prior to proceeding with transplantation. Current or historical donor-specific antibody was occasionally crossed in certain cases at UW and UAB necessitating IVIG/plasmapheresis and/or B cell depletion perioperatively. Some authors raised concerns for cost efficiency given the increased need for organ/specimen transportation, and extensive use of hospital resources and ancillary services. In general, we found that the new allocation system has successfully achieved one of its primary goals-increased kidney transplantation in the disadvantaged, highly sensitized patients; the long-term outcomes in all patients and the cost ramifications of these changes will require continued reassessment and clarification.