Current advances in 2022: A critical review of selected topics by the Association for the Advancement of Blood and Biotherapies (AABB) Clinical Transfusion Medicine Committee.

BACKGROUND: The Association for the Advancement of Blood and Biotherapies Clinical Transfusion Medicine Committee (CTMC) composes a summary of new and important advances in transfusion medicine (TM) on an annual basis. Since 2018, this has been assembled into a manuscript and published in Transfusion. STUDY DESIGN AND METHODS: CTMC members selected original manuscripts relevant to TM that were published electronically and/or in print during calendar year 2022. Papers were selected based on perceived importance and/or originality. References for selected papers were made available to CTMC members to provide feedback. Members were also encouraged to identify papers that may have been omitted initially. They then worked in groups of two to three to write a summary for each new publication within their broader topic. Each topic summary was then reviewed and edited by two separate committee members. The final manuscript was assembled by the first and senior authors. While this review is extensive, it is not a systematic review and some publications considered important by readers may have been excluded. RESULTS: For calendar year 2022, summaries of key publications were assembled for the following broader topics within TM: blood component therapy; infectious diseases, blood donor testing, and collections; patient blood management; immunohematology and genomics; hemostasis; hemoglobinopathies; apheresis and cell therapy; pediatrics; and health care disparities, diversity, equity, and inclusion. DISCUSSION: This Committee Report reviews and summarizes important publications and advances in TM published during calendar year 2022, and maybe a useful educational tool.

Rate of D-alloimmunization in trauma does not depend on the number of RhD-positive units transfused: The BEST collaborative study.

BACKGROUND: Evidence indicates the life-saving benefits of early blood product transfusion in severe trauma resuscitation. Many of these products will be RhD-positive, so understanding the D-alloimmunization rate is important. METHODS: This was a multicenter, retrospective study whereby injured RhD-negative patients between 18-50 years of age who received at least one unit of RhD-positive red blood cells (RBC) or low titer group O whole blood (LTOWB) during their resuscitation between 1 January, 2010 through 31 December, 2019 were identified. If an antibody detection test was performed ≥14 days after the index RhD-positive transfusion then basic demographic information was collected, including whether the patient became D-alloimmunized. The overall D-alloimmunization rate, and the rate stratified by the number of units transfused, were calculated. RESULTS: Data were collected from nine institutions. Five institutions reported fewer than 10 eligible patients each and were excluded. From the remaining four institutions, all from the USA, there were 235 eligible patients; 77 (random effects estimate: 32.7%; 95% CI: 19.1-50.1%) became D-alloimmunized. Three of the institutions reported D-alloimmunization rates ≥38.6%, while the remaining institution's rate was 12.2%. In both random and fixed-effects models, the rate of D-alloimmunization was not significantly different between those who received one RhD-positive unit and those who received multiple RhD-positive units. CONCLUSION: In this large, multicenter study of injured patients, the overall rate of D-alloimmunization fell within the range previously reported. The rate of D-alloimmunization did not increase as the number of transfused RhD-positive units increased. These data can help to inform RhD type selection decisions.

Current advances in transfusion medicine 2021: A critical review of selected topics by the AABB Clinical Transfusion Medicine Committee.

BACKGROUND: Each year the AABB Clinical Transfusion Medicine Committee (CTMC) procures a synopsis highlighting new, important, and clinically relevant studies in the field of transfusion medicine (TM). This has been made available as a publication in Transfusion since 2018. METHODS: CTMC members reviewed and identified original manuscripts covering TM-related topics published electronically (ahead-of-print) or in print from December 2020 to December 2021. Selection of publications was discussed at committee meetings and chosen based on perceived relevance and originality. Next, committee members worked in pairs to create a synopsis of each topic, which was then reviewed by additional committee members. The first and senior authors assembled the final manuscript. Although this synopsis is extensive, it is not exhaustive, and some articles may have been excluded or missed. RESULTS: The following topics are included: blood products; convalescent plasma; donor collections and testing; hemoglobinopathies; immunohematology and genomics; hemostasis; patient blood management; pediatrics; therapeutic apheresis; and cell therapy. CONCLUSIONS: This synopsis highlights and summarizes recent key developments in TM and may be useful for educational purposes.

Risk of ABO-Incompatible Plasma From Non-ABO-Identical Components.

The last several decades have seen significant changes in the approach to resuscitation of bleeding patients. These include the adoption of ABO-incompatible plasma transfusion in the form of group A plasma and/or low titer group O whole blood for trauma patients of unknown ABO group. Studies to date have examined the impact of these practices on patient outcomes and clinical markers of hemolysis in recipients of ABO-incompatible plasma compared to those for whom the plasma is ABO-compatible. Risk for increased mortality and/or overt hemolysis appear to be low among recipients of ABO-incompatible plasma; however, nearly all of studies are retrospective and most have focused only on adult trauma patients so results may not be generalizable to other bleeding patients. Work continues to evaluate the role of various titer thresholds in decreasing hemolytic risk and opportunities remain to improve our understanding of anti-A and anti-B antibody interactions with complement/endothelium and identify strategies to minimize risk.

Neonatal and pediatric blood bank practice in the United States: Results from the AABB pediatric transfusion medicine subsection survey.

BACKGROUND: There are limited standards guiding the selection and processing of blood components specific for neonatal and pediatric transfusions. Therefore, blood banks (BBs) and transfusion services must create their own policies and procedures. STUDY DESIGN AND METHODS: The American Association of Blood Banks (AABB) Pediatric Transfusion Medicine Subsection Committee developed a 74-question survey to capture neonatal and pediatric BB practices in the United States. RESULTS: Thirty-five centers completed the survey: a response rate 15.8%. Responses indicated that most carry a mixed inventory of red blood cells (RBCs); 94.2% allow more than one type of RBC product for small-volume (SV) and large-volume (LV) transfusions to neonatal and pediatric patients. Many had storage age thresholds for RBCs transfused to neonates (SV = 60%, LV = 67.7%) but not older pediatric patients. The use of Group O for nonurgent RBC transfusion in neonates was common (74.2%). Responses related to special processing of RBCs and platelets indicated that 100% RBC and platelets are leukocyte-reduced (LR) for neonates and 97% for non-neonates. Irradiation of RBCs and platelets was commonly performed for neonatal transfusion (88.6%). Providing cytomegalovirus (CMV) seronegative products, volume reduction, and washing were variable. All centers transfused single-donor apheresis platelets; 20% allowed pathogen reduction (PR). The majority of centers have strategies limiting the amount of incompatible plasma transfused; however, few titrate ABO isoagglutinins in plasma-containing products (20% for platelets and 9.1% for plasma). CONCLUSIONS: Variability exists in BB practice for neonatal and pediatric transfusion. Future studies are needed to understand and define best BB practices in these patient populations.

Current advances in transfusion medicine: a 2019 review of selected topics from the AABB Clinical Transfusion Medicine Committee.

BACKGROUND: The AABB Clinical Transfusion Medicine Committee (CTMC) compiles an annual synopsis of the published literature covering important developments in the field of transfusion medicine (TM) for the board of director's review. This synopsis is now made available as a manuscript published in TRANSFUSION. STUDY DESIGN AND METHODS: CTMC committee members review original manuscripts including TM-related topics published in different journals between late 2018 and 2019. The selection of topics and manuscripts are discussed at committee meetings and are chosen based on relevance and originality. After the topics and manuscripts are selected, committee members work in pairs to create a synopsis of the topics, which is then reviewed by two committee members. The first and senior authors of this manuscript assembled the final manuscript. Although this synopsis is comprehensive, it is not exhaustive, and some papers may have been excluded or missed. RESULTS: The following topics are included: infectious risks to the blood supply, iron donor studies, pre-transfusion testing interference and genotyping, cold agglutinin disease (CAD), HLA alloimmunization in platelet transfusions, patient blood management, updates to TACO and TRALI definitions, pediatric TM, and advances in apheresis medicine. CONCLUSION: This synopsis provides easy access to relevant topics and may be useful as an educational tool.

Design and Implementation of a Pathology-Specific Handoff Tool for Residents.

Miscommunication is a source of clinical errors. Tools to decrease the risk of miscommunication (ie, patient handoff tools) are routinely used in clinical specialties that see patients but not routinely used in pathology residency programs. Our primary goal was to develop a structured handoff tool for pathology residents useful for both patient-specific communication and information about general laboratory operation with a secondary goal to increase resident confidence in on-call situations. The CATCH tool was developed and implemented in a pathology residency program with a pre- and postimplementation survey given to residents. The structured handoff tool for pathology residents provided consistent and timely communication between residents and attending physicians. Resident confidence with pathology on-call issues was more likely related to progression through the residency training program rather than implementation of a structured handoff tool.

Seasonal variability is not observed in the rates of high anti-A and anti-B titers in plasma, apheresis platelet, and whole blood units tested by different methods.

BACKGROUND: ABO-incompatible platelet transfusions are common, and transfusions with ABO-incompatible plasma are increasing with the use of group A plasma and group O whole blood (WB) in emergencies. Many centers screen blood products for anti-A and/or anti-B titers to help prevent hemolysis from ABO-incompatible transfusions, yet titer methods and definition of high titers are not standardized. STUDY DESIGN AND METHODS: This international multicenter study collected data on anti-A and anti-B titer practices for plasma, apheresis platelet (AP), and WB units from January 2015 through December 2017 to determine the prevalence of high-titer units using local definitions. RESULTS: A total of 87,701 plasma, AP and WB units were screened for high-titer anti-A and/or anti-B. High-titer detection rates for group A plasma ranged 0%-13.6%; group A AP 2.7%-9.3%; group O AP 2.3%-65.7%; and group O WB 6.4%-20.7%. At the one center that collected group B AP, the high-titer rate was 10.9%. High-titer rates varied from month to month, as well as between years for a given month. There was no clear pattern of when high-titer units were donated. CONCLUSION: The prevalence of high-titer plasma, AP, and WB units varies by titer method and local definition of high titer. Even at the lowest titer threshold of 50, a significant proportion of units had a high-titer antibody, although the clinical relevance of this finding needs further investigation.

Improving the performance of virtual crossmatch results by correlating with nationally-performed physical crossmatches: Obtaining additional value from proficiency testing activities.

PURPOSE: When donor specific HLA antibodies (DSA) are identified, the predictive value of whether a certain strength of reactivity (mean fluorescence intensity, MFI) leads to a positive crossmatch is uncertain. To determine this, we compared the DSA MFI results we generated locally for nationally distributed proficiency samples against the percentage of other laboratories reporting a positive crossmatch. METHOD: DSA MFI from single antigen beads reported by our laboratory for nationally-distributed proficiency testing survey samples was compared against the aggregate percentage of participating laboratories reporting the crossmatch positive using direct, antiglobulin-enhanced microcytotoxic (CDC-AHG), or flow cytometric methods from 2011 to 2015. RESULTS: 180 surveys were analyzed. Positive CDC-AHG and flow cytometric crossmatches were associated with MFI greater than 8554 and 2748 respectively for HLA class I, and 6919 and 3707 respectively for class II. Institutional MFI less than 3000 had high positive predictive values (0.98, 0.85, 0.81) for negative direct, AHG, and flow crossmatches, while MFI greater than 8000 had high negative predictive values for a positive direct, AHG, and flow crossmatches (1.00, 1.00, 0.97). CONCLUSION: Review of locally-generated MFI results as part of participating in proficiency testing allow for predictability of crossmatch results against other laboratories, providing a replicable model for other participating centers.

Routine use of Day 6 and Day 7 platelets with rapid testing: two hospitals assess impact 1 year after implementation.

BACKGROUND: In March 2016 the US Food and Drug Administration published a draft guidance to enhance the safety of platelets (PLTs) for transfusion. Options for hospital transfusion services include the use of rapid testing to extend apheresis PLT dating for up to 7 days. This report describes the impact of routine use of Day 6 and Day 7 PLTs at two hospital transfusion services 1 year after implementation of rapid testing for outdate extension. STUDY DESIGN AND METHODS: PLT transfusion and inventory data were obtained from two hospital-based transfusion services for 12 months before and 12 months after implementation of rapid testing to extend the outdate of apheresis PLTs to 7 days. RESULTS: The outdate rate decreased from 5% to 2% (p < 0.0001) at Hospital 1 and 28% to 14% (p < 0.001) at Hospital 2 after implementation of routine use of Day 6 and Day 7 PLTs. The proportion of apheresis PLT units that underwent secondary screening for bacterial contamination before transfusion in the postimplementation period increased from 33% to 54% at Hospital 1 and from 0% to 31% at Hospital 2. CONCLUSION: A significant decrease in outdate rate was observed after routine use of Day 6 and Day 7 PLTs. Use of rapid testing to extend PLT outdate also resulted in a larger proportion of PLTs that underwent secondary testing for bacterial contamination before transfusion. These observations demonstrate that use of rapid testing to extend apheresis PLT dating up to 7 days enhances the safety of PLTs for transfusion and decreases wastage of a limited resource.

Timing of gamma irradiation and blood donor sex influences in vitro characteristics of red blood cells.

BACKGROUND: There are few studies investigating the effect of irradiation on red blood cells (RBCs) during storage. This study analyzed changes in in vitro quality of RBCs irradiated at several points during storage with the aim of providing evidence to support current maximum pre- and postirradiation storage limits. STUDY DESIGN AND METHODS: Each of seven participating centers produced four pools of 7 standard RBC units (SAGM, AS-3, or PAGGSM), which were then split back into 7 units. All units in a pool were from sex-matched blood donors. Every week during 6 weeks of refrigerated storage, 1 unit was irradiated, while 1 unit was not irradiated (control). Units were tested weekly for biochemical variables, morphology, and mechanical fragility. RESULTS: The earlier during storage that units were irradiated, the higher the hemolysis and K+ at end of storage. Irrespective of the timing of irradiation, there was a rapid increase in extracellular K+ , followed by a more gradual increase in hemolysis. ATP levels decreased faster in irradiated units and were reduced below accepted values if irradiated early. Irradiated female RBCs had an absolute lower hemolysis and K+ level compared to male RBCs at all time points. CONCLUSIONS: The method of blood component manufacturing determined the absolute levels of hemolysis and potassium in irradiated and nonirradiated units, but did not influence the effect that timing of irradiation had on the in vitro quality characteristics. This study provides support for the current Council of Europe guidelines on the time limitations for the irradiation of RBCs.

Addressing the risk of bacterial contamination in platelets: a hospital economic perspective.

BACKGROUND: Bacterially contaminated platelets (PLTs) remain a serious risk. The Food and Drug Administration has issued draft guidance recommending hospitals implement secondary testing or transfuse PLTs that have been treated with pathogen reduction technology (PRT). The cost implications of these approaches are not well understood. STUDY DESIGN AND METHODS: We modeled incurred costs when hospitals acquire, process, and transfuse PLTs that are PRT treated with INTERCEPT (Cerus Corp.) or secondary tested with the PLT PGD Test (Verax Biomedical). RESULTS: Hospitals will spend $221.27 (30.0%) more per PRT-treated apheresis PLT unit administered compared to a Zika-tested apheresis PLT unit that is irradiated and PGD tested in hospital. This difference is reflected in PRT PLT units having: 1) a higher hospital purchase price ($100.00 additional charge compared to an untreated PLT); 2) lower therapeutic effectiveness than untreated PLTs among hematologic-oncologic patients, which contributes to additional transfusions ($96.05); or 3) fewer PLT storage days, which contributes to higher outdating cost from expired PLTs ($67.87). Only a small portion of the incremental costs for PRT-treated PLTs are offset by costs that may be avoided, including primary bacterial culture, secondary bacterial testing ($26.65), hospital irradiation ($8.50), Zika testing ($4.47), and other costs ($3.03). CONCLUSION: The significantly higher cost of PRT-treated PLTs over PGD-tested PLTs should interest stakeholders. For hospitals that outdate PLTs, savings associated with expiration extension to 7 days by adding PGD testing will likely be substantially greater than the cost of implementing PGD-testing. Our findings might usefully inform a hospital's decision to select a particular blood safety approach.

Blood Group Antigen Matching Influence on Gestational Outcomes (AMIGO) study.

BACKGROUND: Red blood cell (RBC) antigen matching policies to prevent alloimmunization in females of childbearing potential (FCP) vary between centers. To inform transfusion centers responsible for making decisions about matching policies for FCPs, the causal stimulus of the antibodies implicated in severe hemolytic disease of the fetus and newborn (HDFN) must be determined. STUDY DESIGN AND METHODS: We conducted a multinational retrospective study of women with offspring affected by severe HDFN requiring neonatal exchange transfusion and/or intrauterine transfusion. Mothers treated at centers that provide extended antigen-negative RBCs (MATCH, five centers) and those that do not (NoMATCH, nine centers) were compared. RESULTS: A total of 293 mothers had at least one affected pregnancy: 179 at MATCH centers and 114 at NoMATCH centers. Most alloimmunization (83%) was attributed to previous pregnancy: 3% to transfusion (two cases at MATCH, six at NoMATCH centers) and 14% undetermined (both antecedent transfusion and pregnancy). Only 50 mothers had received transfusions; 13 had HDFN due to anti-K at MATCH and four at NoMATCH centers. Most (12/13, 92%) of the anti-K HDFN cases at MATCH centers had K+ paternal antigen status. Mothers at the MATCH centers do not appear to be protected from HDFN due to K, C, c, and E antibodies, although the low number of FCPs who received transfusions precluded drawing firm conclusions. CONCLUSION: The causal stimulus of antibodies that cause HDFN is predominantly from previous pregnancy. Although extended RBC matching for FCPs may impart some protection from allosensitization, we were unable to show a positive effect, possibly because matching policies are not uniform and there was a small number of mothers who previously received transfusions.

Massive Transfusion Protocol: Communication Ordering Practice Survey (MTP COPS).

OBJECTIVES: We sought to assess ordering practices and quality of communication during massive transfusion at US level I trauma centers. METHODS: An anonymous, web-based survey was distributed to blood banks supporting US level I trauma centers. Information gathered in the survey included demographics, utilization of and perceived level of support for computerized physician order entry (CPOE), frequency of order confusion, and nonprotocol ordering. Responses were analyzed using descriptive statistics. RESULTS: Responses were received from 43 of 121 centers (35.5% response rate), with the majority completed by blood bank physicians (67.4%) and blood bank supervisors (25.6%). Allowable pathways for massive transfusion protocol (MTP) ordering included CPOE (48.8%), verbal/telephone (86.1%), and written (44.2%). The preferred method of MTP activation was verbal/telephone (86.1%). Initial activation of MTP was well communicated (97.6% agreement), but confusion associated with ongoing needs was reported to occur at least sometimes by 32.6%. CONCLUSIONS: Although CPOE-based MTP ordering is offered by nearly half of US level I trauma centers, verbal/telephone ordering is by far the preferred mechanism. Our survey identifies confusion surrounding blood component needs during MTP resuscitation as an opportunity for practice improvement.

The Crossmatch/Issue Ratio: Use of a Novel Quality Indicator and Results of an International Survey on RBC Crossmatching and Issuing Practices.

OBJECTIVES: To understand the worldwide scope of RBC crossmatching and issuing practices and measure efficiency using a novel quality indicator, the crossmatch/issue (C/I) ratio. METHODS: An electronic survey was disseminated to hospital transfusion services collecting details about RBC crossmatching and issuing practices. Respondents were asked to enumerate the number of RBCs crossmatched and issued at their institutions during the 2014 calendar year to calculate the C/I ratio. RESULTS: Fifty-two survey responses were received, mostly from North American transfusion services (28/52, 54%). The electronic crossmatch was the most common technique (n = 29), and most respondents performed the crossmatch at the time that an order for RBCs was received in the transfusion service (even if an order to issue the RBCs was not received). Data to calculate the C/I ratio were supplied by 22 respondents, and the mean ± SD was 1.30 ± 0.34. There was no difference in C/I ratios between services that use the electronic or serologic crossmatch techniques (P = .49). The ratio was the same at the four sites that crossmatch RBCs at the time of issue compared with the time of order receipt (mean ± SD, 1.11 ± 0.09 vs. 1.35 ± 0.36, respectively; P = .19). CONCLUSIONS: Electronic crossmatching is common, and the C/I ratio can be an indicator of efficiency.

Recent Advances in Preventing Adverse Reactions to Transfusion.

The spectrum of adverse reactions to blood product transfusion ranges from a benign clinical course to serious morbidity and mortality.  There have been many advances in technologies and transfusion strategies to decrease the risk of adverse reactions. Our aim is to address a few of the advancements in increasing the safety of the blood supply, specifically pathogen reduction technologies, bacterial contamination risk reduction, and transfusion associated acute lung injury risk mitigation strategies.