Since the first documented case of SARS‐CoV‐2 infection in the United States in January of 2020, the number of confirmed cases has skyrocketed to over 20,000,000 with more than 350,000 deaths. 1 At the time of this writing, no licensed therapeutics are available despite several clinical trials, including studies of passive antibody therapy. Administration of antibodies against a particular agent to protect or treat susceptible individuals has been used since the 1890s.2 In the context of the COVID‐19 pandemic, anti‐SARS‐CoV‐2 antibody‐containing plasma is obtained by apheresis or separated from whole blood donated by convalescent donors. In March 2020, the FDA published standards for convalescent plasma (CP) donation, and by August 2020 they recognized the potential efficacy of CP with issuance of an emergency use authorization (EUA) for CP in hospitalized COVID‐19 patients. 3 Libster et al. recently showed early administration of high‐titer CP to mildly ill infected older adults reduced the progression of COVID‐19.

The concept that blood has curative qualities dates back to ancient times. The poet Ovid (43 BC–17/18 AD) wrote of the rejuvenation of Aeson by “letting out the old blood” and replacing it with a restorative tincture.1 Accounts of Roman spectators hoping to gain the strength of slain gladiators by drinking their blood are well detailed by the philosopher Pliny the Elder. But it was not until 1829 that James Blundell, the father of modern blood transfusion, published the first successful case of human-to-human blood transfusion, saving the life of a young woman experiencing postpartum hemorrhage by transfusion of 8 ounces of blood (∼240 ml).2 However, many of Blundell’s other patients did not survive transfusion, presumably due to ABO incompatibility and the resulting hemolysis. Recognizing both the benefits and detriments of transfusion, Blundell cautioned that transfusions be limited only to the severely ill.

Background: The Joint Commission lists improving staff communication (handoffs) as part of several National Safety Goals. In this study, we developed an electronic web-based charting system for clinical pathology handoffs, which primarily consist of transfusion medicine calls, and evaluated the advantages over a paper-based handwritten call log. Materials and Methods: A secure online web browser application using Research Electronic Data Capture (REDCap) was designed to document on-call pathology resident consults. A year after implementation, an online survey was administered to our pathology residents in order to evaluate and compare the usability of the electronic application (e-consults) to the previous handwritten call log, which was a notebook where trainees hand wrote different components of the consult. Results: The REDCap web-based application includes discrete fields for patients’ information, requesting physician contact, type of consult, action items for follow-up and faculty responses, as well as other information. These components have eventually progressed to be an online consult call catalog. With approximately 1079 consults per year, transfusion medicine-related calls account for ~90% of the encounters, while clinical chemistry, microbiology and immunology calls constitute the remainder. The overall response rate of the survey was 96% (29 of 30 participants). Of the 16 respondents who experienced both call log systems, 100% responded that REDCap was an improvement over the handwritten call log (P < 0·0001). Conclusion: E-consult documentation entered into a web-based application was a user-friendly, secure clinical information access and effective handoff system as compared to a paper-based handwritten call log.

Technological advances in HLA laboratory testing undoubtedly improved the sensitivity and specificity of HLA antibody assessment but not without introducing a set of challenges regarding data interpretation. In particular, the introduction of solid-phase single-antigen bead (SAB) antibody assessment brought the belief that mean fluorescence intensity (MFI) was a quantifiable value. As such, MFI levels heavily influenced HLA antibody reporting, monitoring, and clinical practice. However, given that SAB testing was neither intended for nor approved to be quantifiable, is the use of MFI in current clinical and laboratory practice valid? What, if anything, does this numerical value actually reveal about the pathogenic potential of the antibody? What are the pitfalls and caveats associated with reporting MFI? Herein, we travel the road to HLA antibody assessment and explore the reliability of MFI values to make clinical decisions.

Recent evidence suggests that belatacept reduces the durability of preexisting antibodies to class I and class II human leukocyte antigens (HLAs). In this case series of 163 highly sensitized kidney transplant candidates whose calculated panel-reactive antibody (cPRA) activity was ≥98% to 100%, the impact of belatacept on preexisting HLA antibodies was assessed. Of the 163 candidates, 72 underwent transplantation between December 4, 2014 and April 15, 2017; 60 of these transplanted patients remained on belatacept consecutively for at least 6 months. We observed a decrease in the breadth and/or strength of HLA class I antibodies as assessed by FlowPRA in belatacept-treated patients compared to controls who did not receive belatacept. Specifically, significant HLA antibody reduction was evident for class I (P <.0009). Posttransplant belatacept-treated patients also had a clinically significant reduction in their cPRA compared to controls (P <.01). Collectively, these findings suggest belatacept can reduce HLA class I antibodies in a significant proportion of highly sensitized recipients and could be an option to improve pretransplant compatibility with organ donors.

The virtual crossmatch (VXM) is gaining acceptance as an alternative approach to assess donor:recipient compatibility prior to transplantation. In contrast to a physical crossmatch, the virtual crossmatch does not require viable donor cells but rather relies on complete HLA typing of the donor and current antibody assessment of the recipient. Thus, the VXM can be performed in minutes which allows for faster transplant decisions thereby increasing the likelihood that organs can be shipped across significant distances yet safely transplanted. Here, we present a brief review of the past 50 years of histocompatibility testing; from the original complement-dependent cytotoxicity crossmatch in 1969 to the new era of molecular HLA typing, solid-phase antibody testing and virtual crossmatching. These advancements have shaped a paradigm shift in our approach to transplantation. That is, foregoing a prospective physical crossmatch in favor of a VXM. In this review, we undertake an in-depth analysis of the pros- and cons- of physical and virtual crossmatching.Finally, we provide objective data on the selected use of the VXM which demonstrate the value of a VXM in lieu of the traditional physical crossmatch for safe and efficient organ transplantation.

Accurate deceased donor HLA typing assumes that the blood sample tested contains only DNA from the organ donor. Prior to procurement, many organ donors are transfused at least one unit of red blood cells (RBC). Non-organ donor DNA acquired from transfusions may result in incorrect and/or ambiguous HLA typing. To address this question, we investigated the impact of RBC transfusion on organ donor HLA typing by using different in vitro transfusion models: leukoreduced (LR) and non-LR RBCs. Various quantities of LR and non-LR RBCs were added to normal peripheral blood and HLA typing was performed by real time PCR. Our results show that HLA typing of deceased donors can be impacted dependent upon the type and quantity of transfused RBCs. Importantly, if LR RBCs are given, HLA typing is unlikely to be affected, precluding the need to delay typing and obtain an alternative source of donor DNA.

The purpose of the STAR 2019 Working Group was to build on findings from the initial STAR report to further clarify the expectations, limitations, perceptions, and utility of alloimmune assays that are currently in use or in development for risk assessment in the setting of organ transplantation. The goal was to determine the precision and clinical feasibility/utility of such assays in evaluating both memory and primary alloimmune risks. The process included a critical review of biologically driven, state-of-the-art, clinical diagnostics literature by experts in the field and an open public forum in a face-to-face meeting to promote broader engagement of the American Society of Transplantation and American Society of Histocompatibility and Immunogenetics membership. This report summarizes the literature review and the workshop discussions. Specifically, it highlights (1) available assays to evaluate the attributes of HLA antibodies and their utility both as clinical diagnostics and as research tools to evaluate the effector mechanisms driving rejection; (2) potential assays to assess the presence of alloimmune T and B cell memory; and (3) progress in the development of HLA molecular mismatch computational scores as a potential prognostic biomarker for primary alloimmunity and its application in research trial design.