A cold case of hemolytic disease of the fetus and newborn resolved by genomic sequencing and population studies to define a new antigen in the Rh system.

BACKGROUND: We report an obstetric case involving an RhD-positive woman who had developed a red blood cell (RBC) antibody that was not detected until after delivery of a newborn, who presented with a positive direct antiglobulin test result. Immunohematology studies suggested that the maternal antibody was directed against a low-prevalence antigen on the paternal and newborn RBCs. RESULTS: Comprehensive blood group profiling by targeted exome sequencing revealed a novel nonsynonymous single nucleotide variant (SNV) RHCE c.486C>G (GenBank MZ326705) on the RHCE*Ce allele, for both the father and newborn. A subsequent genomic-based study to profile blood groups in an Indigenous Australian population revealed the same SNV in 2 of 247 individuals. Serology testing showed that the maternal antibody reacted specifically with RBCs from these two individuals. DISCUSSION: The maternal antibody was directed against a novel antigen in the Rh blood group system arising from an RHCE c.486C>G variant on the RHCE*Ce allele linked to RHD*01. The variant predicts a p.Asn162Lys change on the RhCE protein and has been registered as the 56th antigen in the Rh system, ISBT RH 004063. CONCLUSION: This antibody was of clinical significance, resulting in a mild to moderate hemolytic disease of the fetus and newborn (HDFN). In the past, the cause of such HDFN cases may have remained unresolved. Genomic sequencing combined with population studies now assists in resolving such cases. Further population studies have potential to inform the need to design population-specific red cell antibody typing panels for antibody screening in the Australian population.

Has the frequency of ABO RhD blood groups in Australian blood donors changed as a result of the removal of the variant Creutzfeldt-Jakob disease-based deferral?

BACKGROUND AND OBJECTIVES: Until 25 July 2022, Australians who had spent more than 6 months in the United Kingdom or territories between 1980 and 1996 were deferred from blood donation due to the risk of variant Creutzfeldt-Jakob disease. Removal of this geography-based donor deferral on RhD-negative blood availability has not been reported. MATERIALS AND METHODS: All donors who donated at least once from 25 July 2022 to 25 July 2023 were included. UK donor status, first-time donor and ABO RhD data were extracted from the National Blood Management System. RESULTS: Data from 566,447 blood donors with a valid ABO RhD result were analysed. Of these, 34,560 were new or returning lapsed donors following removal of the UK donor deferral. The median age [range] in years for all donors was 43 [75] with UK donors being older 53 [70]. There was a higher prevalence of RhD-negative status in UK donors (20.2%) compared with first-time blood donors (15.7%). CONCLUSION: UK donors were generally older, female and more likely to be RhD-negative. Although UK donors provided a boost to RhD-negative blood collections, the overall prevalence of ABO RhD blood groups in the total Australian blood donor panel remained similar to previous estimates.

Regular high-frequency whole blood donation and risk of cardiovascular disease in middle-aged and older blood donors in Australia.

BACKGROUND: Previous mixed findings on the associations between whole blood (WB) donation and risk of cardiovascular diseases (CVD) may in part reflect inadequate adjustment for the "healthy donor effect" (HDE). METHODS: We used the Sax Institute's 45 and Up Study linked with blood donation history and other health-related databases to examine the association between regular, high-frequency WB donation and the risk of CVD. To mitigate the impact of HDE, we used a "5-years qualification period," in which donors must donate at least 1 WB donation in the 1st and 5th year of "qualification period." We then compared the risk of CVD in the years following the "qualification period" between the regular high-frequency WB donors (≥2 WB donation in each qualification year) and others using Cox proportional-hazards models. Analyses were adjusted for potential confounders, such as sociodemographic, lifestyle, and health-related variables, and results are reported separately for male and female donors. RESULTS: A total of 2736 male and 2917 female donors were included in the analyses. The median years of follow-up per donor was 5.84 years (Q1-Q3, 5.47-6.23). The rate of CVD hospitalization was 11.20 and 4.50 per 1000 person-years for males and females, respectively. In fully adjusted models, the risk (hazard ratio) of CVD in regular high-frequency donors compared to other donors was 0.93 (95% Confidence Interval (CI), 0.68-1.29) for males and 0.79 (95% CI, 0.49-1.28) for females. CONCLUSIONS: We did not observe a statistically significant reduction of CVD risk in regular, high-frequency WB donors when adjusted for potential confounders.

Absence of correlation between ABO Rh(D) blood group and neutralizing antibody titers in SARS-CoV-2 convalescent plasma donors.

BACKGROUND: Several studies have described associations between ABO blood group and SARS-CoV-2 infection severity in hospitalized patients where group A individuals are over-represented and group O individuals may have a lower infection rate. In convalescent individuals, group B blood donors have higher neutralizing SARS-CoV-2 antibody titers. We analyzed whether there was any correlation of ABO Rh(D) blood group with SARS-CoV-2 infection and with neutralizing antibodies in Australian convalescent plasma (CP) donors. STUDY DESIGN AND METHODS: ABO Rh(D) distribution and demographics of CP donors (n = 765) were compared with the total blood donor panel (n = 488,028), plasmapheresis donors (n = 203,176) and whole blood donors (n = 282,437) from 2020. The presence of neutralizing antibodies in CP donors was measured using the Vero E6 cell microneutralization assay. RESULTS: The distribution of ABO group in CP donors compared to the total donor panel was not significantly different (p = .177). There were significantly more group AB donors in the plasmapheresis subset (p = .005) and group O individuals were over-represented in the whole blood donor subset (p < .0001). There was no significant difference in neutralizing antibody levels among CP donors with differing ABO blood groups (p = .872). CONCLUSION: ABO Rh(D) blood group distribution was not found to be significantly different between convalescent plasma donors and general blood donors in our large sample group. Inherent blood donor selection biases associated with clinical demand accounted for some differences within CP donors. The levels of SARS-CoV-2 neutralizing antibodies were also not significantly associated with ABO Rh(D) group.

The distribution of ABO RhD blood groups in Australia, based on blood donor and blood sample pathology data.

OBJECTIVE: To determine the distribution of ABO RhD blood groups in Australia in 2019. DESIGN: Retrospective analysis of blood group data for blood donors (Australian Red Cross Lifeblood National Blood Management System) and for people whose blood type was determined in samples submitted for analysis by hospital-based or private pathology agencies. SETTING: All Australian states and territories, 1 January - 31 December 2019. MAIN OUTCOME MEASURES: Proportions of donors and patients, by ABO blood group and RhD status. These proportions were compared with published data for 1993-94 first-time blood donors. RESULTS: A total of 1 318 751 valid ABO RhD blood group results were provided by 28 of 41 invited pathology agencies (including 245 of 324 approved health providers, 76%). Valid ABO RhD data were available for 490 491 blood donors, including 103 798 first-time donors (21.2%). Blood group prevalence based on samples typed by pathology services was O RhD+, 38.4%; O RhD-, 6.5%; A RhD+, 32.0%; A RhD-, 5.6%; B RhD+, 11.8%; B RhD-, 1.5%; AB RhD+, 3.7%; and AB RhD-, 0.5% (totals: RhD+, 85.9%; RhD-, 14.1%). The distribution based on typing of first-time blood donors was similar. The overall proportion of RhD+ first-time donors rose from 81% in 1993-94 to 83.8% in 2019; the proportion of groups B and AB RhD+ RBC units issued declined from 9.8% in 2010-11 to 6.9% of all RBC units in 2019-20, while that of O RhD- RBC units increased from 11.7% to 17.4%. CONCLUSION: Our national assessment of ABO RhD prevalence in Australia provides updated information for re-evaluating blood and blood product collection and holdings in light of changes in population demographic characteristics.

SARS-CoV-2 neutralizing antibodies: Longevity, breadth, and evasion by emerging viral variants.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)-confirmed Coronavirus Disease 2019 (COVID-19) individuals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of "high responders" maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design.

Long-term return and donation pattern of those who begin donating at different ages: A retrospective cohort analysis of blood donors in Australia.

BACKGROUND: This study compared the likelihood of return to donate and donation rate ratio by age of donors at their first donation when followed up to 12 years. STUDY DESIGN AND METHODS: Donation history of two cohorts of first-time donors (those donating in 2007 and 2013) was extracted until March 2019 from Australian Red Cross Lifeblood's national database. Poisson regression analyses compared donor return and negative-binomial regression estimated the rate ratio of donations. RESULTS: A total of 120 469 and 95 381 donors were included in the 2007 and 2013 cohorts, respectively. Compared to donors aged 20-24 years, the likelihood of return in both cohorts increased consistently as age at first donation increased from 30-years and above. Average number of whole-blood and plasmapheresis donations increased as the age at first donation increased from 30-years onward. The whole-blood donation rate was highest for donors ≥60 years, while plasmapheresis donation rate was highest for donors aged 50-59 years. These patterns were largely consistent when stratified by sex. CONCLUSIONS: To continuously ensure the short- to mid-term sufficiency of blood supply in Australia, targeted recruitment of donors aged 30-years and above may be considered, however its feasibility and impact should be explored further given relatively smaller proportion of new donors are middle-aged and older under current policies. Future studies with a longer follow-up period are needed to examine whether the frequency of donation among those who start donating at a younger age increases later in their life when they are 30-years or over.

Visits to general practitioners after iron-related deferrals from blood donation in middle-aged and older Australian blood donors.

BACKGROUND: Australian Red Cross Lifeblood (Lifeblood) advises donors to visit their general practitioner (GP) for medical follow-up if they are deferred from donating due to having a lower than acceptable level of hemoglobin (Hb) and/or serum ferritin (iron-related deferrals). METHODS: We used the Sax Institute's 45 and Up Study data linked to Lifeblood's donor datasets and other health administrative datasets. We examined the rate of visits to a GP after iron-related deferral from donation, and investigated whether an early visit to a GP (within 30 days following the deferral) had an impact on return to make successful donation within 12, 18, and 24 months compared to a delayed or no GP visit. RESULTS: A total of 1928 donors underwent iron-related deferral. The rate of visits to a GP in the first month after deferral was double the rate observed a month prior. However, only 52.4% of those deferred visited a GP early with slightly more than half of those receiving an iron-monitoring test. Return to donate over the 24 months was lower in donors visiting their GP early (adjusted Hazard Ratio [aHR] 0.86, 95% CI 0.77-0.97). Early GP visitors were likely to have a relatively poorer health than the delayed or no GP visit group. CONCLUSIONS: Only half of the donors with an iron-related deferral followed advice from Lifeblood and visited their GP within 30 days of deferral, and these donors have a significantly reduced likelihood of future successful blood donation which may be due to their relatively poorer health status.

Willingness of blood donors in Australia to provide additional data and blood sample for health research.

BACKGROUND: Many blood collection agencies are generating important data on donor health outcomes using large-scale blood donor cohort studies. Such studies can be very effective when donors provide access to linkage of their data to external health databases, and storage and genomic testing of their blood sample. In this study, we aimed to assess the willingness of Australian blood donors to provide additional data and blood sample for donation-related and other health research. STUDY DESIGN AND METHODS: We invited 2017 donors to complete a survey using four methods (postal letter, postal letter and email, email only, and in-center recruitment). The survey asked for information on demographics, lifestyle behaviors, health, experience and attitude to blood donation, and willingness to give blood sample and additional data for research. RESULTS: Response rates ranged from 23.8% for email only to 77.2% for in-center recruitment. Of those who responded (n = 827), 95.5% indicated they would be willing to provide a blood sample for donation and transfusion-related research. Of these, >90.0% were willing for their sample to be used in research involving genetic testing and other health-related topics. Also, >90.0% were willing to consent for linkage of their information to external health databases. CONCLUSIONS: Donors surveyed reported a high willingness to participate in health research by completing surveys, allowing linkage to external datasets, and providing a blood sample. These findings provide strong support for future longitudinal research studies with Australian blood donors.

An international comparison of HIV prevalence and incidence in blood donors and general population: a BEST Collaborative study.

BACKGROUND AND OBJECTIVES: Efficiency in mitigating HIV transmission risk by transfusion may vary internationally. We compared HIV prevalence and incidence in blood donors across different jurisdictions in relation to those rates in the general population and differences in deferral practices. MATERIALS AND METHODS: Data from 2007 to 2016 were collected in Australia, Brazil (São Paulo), Canada, England, France, Italy, Ireland, Japan, the Netherlands, New Zealand, Norway, Spain (Basque Country), USA (Vitalant) and Wales. For each country/region, the number of HIV antibody-positive donations and nucleic acid testing (NAT)-only-positive donations was broken down according to first-time or repeat donor status, along with the relevant denominators. RESULTS: There is a modest correlation between HIV prevalence among first-time donors and HIV prevalence in the general population. However, rates of HIV-positive donations in repeat donors, a proxy for incidence, do not correlate with incidence rates in the general population. Rates in donors from Italy and Basque Country, where deferral criteria for men having sex with men are less stringent, are higher compared with most other jurisdictions. Rates of NAT-only-positive donations are extremely low and do not differ significantly after adjustment for multiple comparisons. CONCLUSION: Donor HIV rates are only weakly associated with those observed in the general population. Countries with less stringent deferral criteria have higher HIV rates in their donor population, but the rates remain very low.

Seroprevalence of SARS-CoV-2-specific antibodies in Sydney after the first epidemic wave of 2020.

OBJECTIVES: To estimate SARS-CoV-2-specific antibody seroprevalence after the first epidemic wave of coronavirus disease 2019 (COVID-19) in Sydney. SETTING, PARTICIPANTS: People of any age who had provided blood for testing at selected diagnostic pathology services (general pathology); pregnant women aged 20-39 years who had received routine antenatal screening; and Australian Red Cross Lifeblood plasmapheresis donors aged 20-69 years. DESIGN: Cross-sectional study; testing of de-identified residual blood specimens collected during 20 April - 2 June 2020. MAIN OUTCOME MEASURE: Estimated proportions of people seropositive for anti-SARS-CoV-2-specific IgG, adjusted for test sensitivity and specificity. RESULTS: Thirty-eight of 5339 specimens were IgG-positive (general pathology, 19 of 3231; antenatal screening, 7 of 560; plasmapheresis donors, 12 of 1548); there were no clear patterns by age group, sex, or location of residence. Adjusted estimated seroprevalence among people who had had general pathology blood tests (all ages) was 0.15% (95% credible interval [CrI], 0.04-0.41%), and 0.29% (95% CrI, 0.04-0.75%) for plasmapheresis donors (20-69 years). Among 20-39-year-old people, the age group common to all three collection groups, adjusted estimated seroprevalence was 0.24% (95% CrI, 0.04-0.80%) for the general pathology group, 0.79% (95% CrI, 0.04-1.88%) for the antenatal screening group, and 0.69% (95% CrI, 0.04-1.59%) for plasmapheresis donors. CONCLUSIONS: Estimated SARS-CoV-2 seroprevalence was below 1%, indicating that community transmission was low during the first COVID-19 epidemic wave in Sydney. These findings suggest that early control of the spread of COVID-19 was successful, but efforts to reduce further transmission remain important.

Understanding the demand for phenotyped red blood cell units and requests to perform molecular red blood cell typing for Australian patients.

BACKGROUND: Australian Red Cross Lifeblood has seen a 50 % increase in demand for phenotyped red blood cell (RBC) units between 2016-2018 and a 30 % increase in demand in 2018 to perform molecular RBC typing on patient samples. Lifeblood conducted a survey to understand transfusion laboratory practices for requesting patient phenotyping and/or molecular RBC typing and for selecting phenotyped RBC units in various patient groups. STUDY DESIGN AND METHODS: An electronic Qualtrics survey form was sent to 296 transfusion laboratories with questions designed to understand the practice of selecting phenotyped RBC units and reasons for requesting extended serology or molecular RBC typing. RESULTS: 49 (16.6 %) transfusion laboratories provided data. Reasons to request extended phenotyping and/or molecular RBC typing for patients included; chronic transfusion (n = 31 laboratories), sickle cell disease (n = 25), Thalassemia (n = 23), requirement for anti-CD38 or other MAB therapy (n = 23) or Myelodysplasia (n = 22). Forty-seven transfusion laboratories provided responses with reasons for requesting molecular RBC typing which included: predicting phenotype in patients with multiple antibodies (n = 31), prior to administering anti-CD38 or other MAB therapies (n = 29), for pregnancy related transfusions (n = 28) or for confirming the phenotype of recently transfused patients (n = 18). CONCLUSION: Transfusion laboratory practices indicated that phenotyped RBC units were selected for patients requiring chronic transfusion support and/or undergoing MAB therapy. Requests for molecular RBC typing occurred for more complex patient requirements where serological investigations were not suitable or possible due to reagent restrictions.

Age of Red Cells for Transfusion and Outcomes in Critically Ill Adults.

BACKGROUND: It is uncertain whether the duration of red-cell storage affects mortality after transfusion among critically ill adults. METHODS: In an international, multicenter, randomized, double-blind trial, we assigned critically ill adults to receive either the freshest available, compatible, allogeneic red cells (short-term storage group) or standard-issue (oldest available), compatible, allogeneic red cells (long-term storage group). The primary outcome was 90-day mortality. RESULTS: From November 2012 through December 2016, at 59 centers in five countries, 4994 patients underwent randomization and 4919 (98.5%) were included in the primary analysis. Among the 2457 patients in the short-term storage group, the mean storage duration was 11.8 days. Among the 2462 patients in the long-term storage group, the mean storage duration was 22.4 days. At 90 days, there were 610 deaths (24.8%) in the short-term storage group and 594 (24.1%) in the long-term storage group (absolute risk difference, 0.7 percentage points; 95% confidence interval [CI], -1.7 to 3.1; P=0.57). At 180 days, the absolute risk difference was 0.4 percentage points (95% CI, -2.1 to 3.0; P=0.75). Most of the prespecified secondary measures showed no significant between-group differences in outcome. CONCLUSIONS: The age of transfused red cells did not affect 90-day mortality among critically ill adults. (Funded by the Australian National Health and Medical Research Council and others; TRANSFUSE Australian and New Zealand Clinical Trials Registry number, ACTRN12612000453886 ; ClinicalTrials.gov number, NCT01638416 .).

Comparison of group O Rh(D)- red blood cell use in pregnant women across hospitals of various sizes and obstetric capabilities prior to the introduction of patient blood management guidelines.

BACKGROUND: O Rh(D)- red blood cell (RBC) units can generally be transfused to most patients regardless of their ABO blood type and are frequently used during emergency situations. Detailed usage patterns of O Rh(D)- RBC units in obstetric populations have not been well characterised. With the introduction of patient blood management guidelines, historical usage patterns are important for providing comparative data. AIMS: To determine how the use of O Rh(D)- RBC units in pregnant women differs between hospitals of different sizes and obstetric capabilities prior to patient blood management guidelines. METHODS: Data from 67 New South Wales public hospital blood banks were linked with hospital and perinatal databases to identify RBC transfusions during pregnancy, birth and postnatally between July 2006 and December 2010. RBC transfusions were divided into O Rh(D)- or other blood types. Hospitals were classified according to birth volume, obstetric capability and location, with transfusions classified by timing and diagnosis. RESULTS: Of the 12 078 RBC units transfused into pregnant women, 1062 (8.8%) were O Rh(D)-. Higher use of O Rh(D)- RBC units was seen in antenatal transfusions, preterm deliveries and in regional or smaller hospitals. There was wide variation in rates of O Rh(D)- RBC transfusion among hospitals. CONCLUSIONS: The rate of O Rh(D)- RBC unit use in obstetrics was lower during the period assessed than the nationally reported usage. It is encouraging that O Rh(D)- RBCs were more commonly used in emergency or specialised situations, or in facilities where holding a large blood inventory is not feasible.

Fresh Red Cells for Transfusion in Critically Ill Adults: An Economic Evaluation of the Standard Issue Transfusion Versus Fresher Red-Cell Use in Intensive Care (TRANSFUSE) Clinical Trial.

OBJECTIVES: Trials comparing the effects of transfusing RBC units of different storage durations have considered mortality or morbidity as outcomes. We perform the first economic evaluation alongside a full age of blood clinical trial with a large population assessing the impact of RBC storage duration on quality-of-life and costs in critically ill adults. DESIGN: Quality-of-life was measured at 6 months post randomization using the EuroQol 5-dimension 3-level instrument. The economic evaluation considers quality-adjusted life year and cost implications from randomization to 6 months. A generalized linear model was used to estimate incremental costs (2016 U.S. dollars) and quality-adjusted life years, respectively while adjusting for baseline characteristics. SETTING: Fifty-nine ICUs in five countries. PATIENTS: Adults with an anticipated ICU stay of at least 24 hours when the decision had been made to transfuse at least one RBC unit. INTERVENTIONS: Patients were randomized to receive either the freshest or oldest available compatible RBC units (standard practice) in the hospital transfusion service. MEASUREMENTS AND MAIN RESULTS: EuroQol 5-dimension 3-level utility scores were similar at 6 months-0.65 in the short-term and 0.63 in the long-term storage group (difference, 0.02; 95% CI, -0.00 to 0.04; p = 0.10). There were no significant differences in resource use between the two groups apart from 3.0 fewer hospital readmission days (95% CI, -5.3 to -0.8; p = 0.01) during follow-up in the short-term storage group. There were no significant differences in adjusted total costs or quality-adjusted life years between the short- and long-term storage groups (incremental costs, -$2,358; 95% CI, -$5,586 to $711) and incremental quality-adjusted life years: 0.003 quality-adjusted life years (95% CI, -0.003 to 0.008). CONCLUSIONS: Without considering the additional supply cost of implementing a freshest available RBC strategy for critical care patients, there is no evidence to suggest that the policy improves quality-of-life or reduces other costs compared with standard transfusion practice.

Completeness and accuracy of self-reported history of blood donation: results from a cohort of older adults in Australia.

BACKGROUND: The validity of studies relying on self-report of blood donation may be severely threatened by systematic errors. STUDY DESIGN AND METHODS: We linked the Sax Institute's 45 and Up Study data, which asked self-report of blood and plasma donation including the date of most recent donation to the blood donor database at the Australian Red Cross Blood Service. We used the linked data to validate the accuracy of self-reported blood donation history including the completeness and accuracy of reported date of most recent donation. RESULTS: Of the total 142,503 participants, 47.8 and 5.1% reported ever donating blood and plasma, respectively. Of those self-reporting blood donation (n = 23,113) and plasma donation (n = 4,451) within the last 10 years of survey, 6262 (27.1%) and 1444 (33.0%) had no record of donation within that period, respectively. Among those who had a record of blood and plasma donation within 10 years before the survey, 97.6 and 93.0% correctly self-reported ever donating blood and plasma, respectively. Donors consistently reported a donation date more recent than the actual recorded date, and the median discrepancy and variability increased as the length of time from the survey date to the actual date of donation increased. CONCLUSIONS: Almost 98% of donors donating blood within a decade of survey completion date can correctly self-report their history of donation as ever donating blood, whereas 27% of participants self-reporting donation within a decade may not have actually donated blood. Further, self-reported date of blood donation is not a reliable measure of actual date of donation.

Safety of blood donation by individuals over age 70 and their contribution to the blood supply in five developed countries: a BEST Collaborative group study.

BACKGROUND: Some countries impose an upper age limit on whole blood and double RBC donation while others do not. We evaluated the safety of blood donation in older individuals (≥71 years), and their contribution to the blood supply of five countries. STUDY DESIGN AND METHODS: Twelve blood center members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative from four countries with no upper age limit for whole blood and double RBC donation (Canada, New Zealand, England, and the United States) or an upper age limit of 80 (Australia) provided 2016 data on donors and donations, deferral rates, and vasovagal reactions by donor age and sex. Donors under age 24 were included in the number of total donors and donations, but not in deferral and reaction rate comparisons. RESULTS: Older donors accounted for 1.0% (New Zealand) to 4.3% (United States) of donors, and 1.5% (New Zealand) to 5.6% (United States) of donations; most were between ages 71 and 76. The deferral rate was higher in older compared to 24- to 70-year-old males, but very similar between older and younger females. In contrast, vasovagal reaction rates were either lower (male donors) or similar (female donor for reactions with loss of consciousness) in older compared to 24- to 70-year-old donors. CONCLUSIONS: Exclusion solely based on older age appears to be unwarranted based on safety concerns such as donor reactions. Healthy older individuals can continue to safely donate and make a significant contribution to the blood supply past arbitrary age limits.

A randomized, controlled pilot clinical trial of cryopreserved platelets for perioperative surgical bleeding: the CLIP-I trial (Editorial, p. 2759).

BACKGROUND: Cryopreservation extends platelet (PLT) shelf life from 5 to 7 days to 2 to 4 years. However, only 73 patients have been transfused cryopreserved PLTs in published randomized controlled trials (RCTs), making safety data insufficient for regulatory approval. STUDY DESIGN AND METHODS: The Cryopreserved vs. Liquid Platelet (CLIP) study was a double-blind, pilot, multicenter RCT involving high-risk cardiothoracic surgical patients in four Australian hospitals. The objective was to test, as the primary outcome, the feasibility and safety of the protocol. Patients were allocated to study group by permuted block randomization, with patients and clinicians blinded by use of an opaque shroud placed over each study PLT unit. Up to 3 units of cryopreserved or liquid-stored PLTs were administered per patient. No other aspect of patient care was affected. Adverse events were actively sought. RESULTS: A total of 121 patients were randomized, of whom 23 received cryopreserved PLTs and 18 received liquid-stored PLTs. There were no differences in blood loss (median, 715 mL vs. 805 mL at 24 hr; difference between groups 90 mL [95% CI, -343.8 to 163.8 mL], p = 0.41), but the Bleeding Academic Research Consortium criterion for significant postoperative hemorrhage in cardiac surgery composite bleeding endpoint occurred in nearly twice as many patients in the liquid-stored group (55.6% vs. 30.4%, p = 0.10). Red blood cell transfusion requirements were a median of 3 units in the cryopreserved group versus 4 units with liquid-stored PLTs (difference between groups, 1 unit [95% CI, -3.1 to 1.1 units]; p = 0.23). Patients in the cryopreserved group were more likely to be transfused fresh-frozen plasma (78.3% vs. 27.8%, p = 0.002) and received more study PLT units (median, 2 units vs. 1 unit; difference between groups, 1 unit [95% CI, -0.03 to 2.0 units]; p = 0.012). There were no between-group differences in potential harms including deep venous thrombosis, myocardial infarction, respiratory function, infection, and renal function. No patient had died at 28 days, and postoperative length of stay was similar in each group. CONCLUSION: In this pilot RCT, compared to liquid-stored PLTs, cryopreserved PLTs were associated with no evidence of harm. A definitive study testing safety and hemostatic effectiveness is warranted.

Mortality and hospital readmissions in the first year of life after intra-uterine and neonatal blood product transfusions: A population data linkage study.

AIM: Blood product transfusions are a potentially life-saving therapy for fetal and neonatal anaemia, but there is limited population-based research on outcomes. We aimed to describe mortality, readmission and average hospital stay in the first year of life for infants with or without intra-uterine or neonatal blood product transfusions. METHODS: Linked birth, hospital and deaths data from New South Wales, Australia (January 2002-June 2014) were used to identify singleton infants (≥23 weeks' gestation, surviving to 29 days; n = 1 089 750) with intra-uterine or neonatal transfusion or no transfusion. Rates of mortality and readmission in the first year (29-365 days) and days in hospital were calculated. RESULTS: Overall, 68 (0.06/1000) infants had experienced intra-uterine transfusion and 4332 (3.98/1000) neonatal transfusion. Transfusion was more common among those born at earlier gestational ages requiring invasive ventilation. Mortality, readmissions and average days in hospital were higher among transfused than non-transfused infants. Over half of infants with intra-uterine and neonatal transfusion had ≥1 readmission in the first 29-365 days (55.9 and 51.8%, respectively), and around a quarter had ≥2 (20.6 and 28.5%, respectively) compared with 15.3% with ≥1 and 3.5% with ≥2 in the non-transfused group. CONCLUSION: Infants with a history of blood product transfusion, particularly those needing a neonatal transfusion, had higher mortality and more frequent contact with the hospital system in the first year of life than those infants with no history of transfusion.