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.

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.

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.

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.

Seasonal distribution of severe ADAMTS13 deficient idiopathic thrombotic thrombocytopenic purpura.

BACKGROUND: Idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare yet potentially fatal thrombotic microangiopathy. Severe deficiency of ADAMTS13 activity via autoantibody formation has been associated with idiopathic TTP; however, specific triggers are poorly defined. Previous studies have reported seasonal associations of TTP, with warm-weather seasons appearing to have the strongest predilection. We characterized the seasonal distribution of severe ADAMTS13 deficient idiopathic TTP at our multi-hospital institution. METHODS: Apheresis records from 2005-2012 were queried for patients with a clinical diagnosis of TTP, accompanying pre-plasmapheresis ADAMTS13 activity <10%, and no other explanations for thrombotic microangiopathy. Date of admission and ADAMTS13 activity were collected. Both initial episodes and relapses in patients whose initial episodes occurred since 2005 were included in the analysis. Goodness-of-fit chi-square analysis was performed and statistical significance was defined as p<0.05. RESULTS: Of 237 consecutive new patients with a suspected clinical diagnosis of TTP, 73 patients met inclusion criteria and had a total of 110 unique presentations for either initial TTP episodes or TTP relapses. Sixteen patients had 37 relapses of their idiopathic TTP (range 1-7). No statistically significant seasonal or monthly associations were identified with either initial or any TTP episodes. CONCLUSION: A seasonal association of severe ADAMTS13 deficient idiopathic TTP was not observed. Unknown variables may explain previous observations of seasonal associations of idiopathic TTP in other regions of the United States. Thus, individual institutions should characterize their own seasonal distributions of idiopathic TTP as part of the exploration of possible disease triggers in their respective areas.

Routine use of a rapid test to detect bacteria at the time of issue for nonleukoreduced, whole blood-derived platelets.

BACKGROUND: The Pan Genera detection (PGD) test is used to screen platelet (PLT) products for bacterial contamination. We report the experience of using the PGD test on whole blood-derived PLTs (WBPs) at two large centralized transfusion services (CTS). STUDY DESIGN AND METHODS: Records of PGD test results were retrospectively reviewed. The PGD test was performed on individual WBP units or pools of WBPs ranging in size from 2 to 6 units at the time of issue. Bacterial culture was performed on PLT products with positive PGD tests, and at one CTS, the available cocomponents. RESULTS: A total of 70,561 WBP pools were screened with the PGD test. There were seven true-positive PGD tests and 242 false-positive tests (positive predictive value of PGD test, 2.81%). The overall contamination rate was 99 per 10(6) WBP pools (1:10,080; 95% confidence interval [CI], 40-204), and the false-positive rate was 3430 per 10(6) WBP pools (1:292; 95% CI, 3011-3890). All seven bacterial isolates were Gram positive. The median age of the individual WBP units in the seven contaminated pools was 5 days (range, 3-5 days) compared to 4 days (range, 1-5 days) in the false-positive pools (p=0.0012). The same bacteria isolated from a positive PLT pool also grew in one red blood cell cocomponent. CONCLUSION: After testing more than 70,000 WBP pools at two large CTSs, the rate of contaminated WBP pools detected by the PGD test was 99 per 10(6) pools (1:10,080).

Platelet transfusion - the art and science of compromise.

SUMMARY: Many modern therapies depend on platelet (PLT) transfusion support. PLTs have a 4- to 7-day shelf life and are frequently in short supply. In order to optimize the inventory PLTs are often transfused to adults without regard for ABO compatibility. Hemolytic reactions are infrequent despite the presence of 'high titer' anti-A and anti-B antibodies in some of the units. Despite the low risk for hemolysis, some centers provide only ABO identical PLTs to their recipients; this practice might have other beneficial outcomes that remain to be proven. Strategies to mitigate the risk of hemolysis and the clinical and laboratory outcomes following ABO-matched and mismatched transfusions will be discussed. Although the PLTs themselves do not carry the D antigen, a small number of RBCs are also transfused with every PLT dose. The quantity of RBCs varies by the type of PLT preparation, and even a small quantity of D+ RBCs can alloimmunize a susceptible D- host. Thus PLT units are labeled as D+/-, and most transfusion services try to prevent the transfusion of D+ PLTs to D- females of childbearing age. A similar policy for patients with hematological diseases is controversial, and the elements and mechanisms of anti-D alloimmunization will be discussed.

Changes in mechanical fragility and free hemoglobin levels after processing salvaged cardiopulmonary bypass circuit blood with a modified ultrafiltration device.

Modified ultrafiltration (MUF) is available for the salvage of post-cardiopulmonary bypass circuit blood. This study evaluated the extent of hemolysis, the mechanical fragility index (MFI), and the amount of plasma free hemoglobin (PFHb) created after processing with the MUF device. Several RBC parameters were measured on pre- and post-MUF device processed samples of blood from 12 patients undergoing cardiac surgery. The MFI and total amount of PFHb did not change significantly between the pre- and post-processing samples: MFI, pre: .19 +/- .06 versus post: .19 +/- .06, p = .76; total amount of PFHb, pre: .24 +/- .21 g versus post: .20 +/- .12 g, p = .42. There was significantly more hemolysis in the post-processing samples compared with the pre-processing samples, .33 +/- .24% versus .96 +/- .48%, respectively, p < .001. Although percent hemolysis was increased following processing with the MUF device, the total amount of PFHb and RBC sublethal injury were not increased. The clinical significance of these findings needs to be determined.

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.

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.

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.

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.