Donor pregnancies and transfusion recipient mortality: A role for red blood cell storage?

BACKGROUND AND OBJECTIVES: Donor characteristics have been implicated in transfusion-related adverse events. Uncertainty remains about whether sex, and specifically pregnancy history of the blood donor, could affect patient outcomes. Whether storage duration of the blood product could be important for patient outcomes has also been investigated, and a small detrimental effect of fresh products remains a possibility. Here, we hypothesize that fresh red blood cell products donated by ever-pregnant donors are associated with mortality in male patients. MATERIALS AND METHODS: We used data from a cohort study of adult patients receiving a first transfusion between 2005 and 2015 in the Netherlands. The risk of death after receiving a transfusion from one of five exposure categories (female never-pregnant stored ≤10 days, female never-pregnant stored >10 days, female ever-pregnant stored ≤10 days, female ever-pregnant stored >10 days and male stored for ≤10 days), compared to receiving a unit donated by a male donor, which was stored for >10 days (reference), was calculated using a Cox proportional hazards model. RESULTS: The study included 42,456 patients who contributed 88,538 person-years in total, of whom 13,948 died during the follow-up of the study (33%). Fresh units (stored for ≤10 days) from ever-pregnant donors were associated with mortality in male patients, but the association was not statistically significant (hazard ratio 1.39, 95% confidence interval 0.97-1.99). Sensitivity analyses did not corroborate this finding. CONCLUSION: These findings do not consistently support the notion that the observed association between ever-pregnant donor units and mortality is mediated by blood product storage.

Efficacy and safety of platelet additive solution-E stored platelet concentrates.

INTRODUCTION: In 2018, platelet (PLT) additive solution-E (PAS-E) was introduced. The implementation of PAS-E was expected to diminish the number of allergic reactions in recipients following a PLT transfusion. Here, we evaluated the efficacy and safety of transfusions with PLTs stored in PAS-E. STUDY DESIGN AND METHODS: After implementation of PAS-E, data were collected from 2 cohorts of patients with hematological disorders as well as oncology patients, receiving PLTs in PAS-E. A similar patient group in a recent RCT, receiving PLTs in plasma, was used as a historical control group for both cohorts. Endpoints were corrected count increments (CCIs), bleeding scores (only reported in cohort 1), and the incidence of adverse reactions. RESULTS: In cohort 1, the mean 1-h CCI was 14.3 ± 6.9, and the 24-h CCI was 8.7 ± 5.6. In cohort 2, the 1-h CCI was 11.6 ± 7.8 and the 24-h CCI was 7.0 ± 6.1. In the control group, the 1-h CCI was 15.4 ± 5.5 and 24-h CCI 8.7 ± 4.8. Bleeding complications of WHO grade ≥2 occurred in 40% of patients in cohort 1 compared to 44% in plasma PCs. The incidence of adverse reactions was 1.2% in the two PAS-E cohorts, compared to 3.0% in plasma PCs. National hemovigilance data showed a significant reduction in allergic reactions with PAS-E PC transfusions as compared to plasma PCs with an odds ratio of 0.46 (CI 95% 0.37-0.58). CONCLUSION: The CCIs of PLTs in PAS-E were decreased compared to plasma PCs, but clinically acceptable. Allergic transfusion reactions were decreased in PAS-E PCs compared to plasma PCs.

The haemostatic effect of deep-frozen platelets versus room temperature-stored platelets in the treatment of surgical bleeding: MAFOD-study protocol for a randomized controlled non-inferiority trial.

BACKGROUND: The Netherlands Armed Forces have been successfully using deep-frozen (- 80 °C) thrombocyte concentrate (DTC) for the treatment of (massive) bleeding trauma patients in austere environments since 2001. However, high-quality evidence for the effectiveness and safety of DTCs is currently lacking. Therefore, the MAssive transfusion of Frozen bloOD (MAFOD) trial is designed to compare the haemostatic effect of DTCs versus room temperature-stored platelets (RSP) in the treatment of surgical bleeding. METHODS: The MAFOD trial is a single-blinded, randomized controlled non-inferiority trial and will be conducted in three level 1 trauma centres in The Netherlands. Patients 12 years or older, alive at hospital presentation, requiring a massive transfusion including platelets and with signed (deferred) consent will be included. The primary outcome is the percentage of patients that have achieved haemostasis within 6 h and show signs of life. Haemostasis is defined as the time in minutes from arrival to the time of the last blood component transfusion (plasma/platelets or red blood cells), followed by a 2-h transfusion-free period. This is the first randomized controlled study investigating DTCs in trauma and vascular surgical bleeding. DISCUSSION: The hypothesis is that the percentage of patients that will achieve haemostasis in the DTC group is at least equal to the RSP group (85%). With a power of 80%, a significance level of 5% and a non-inferiority limit of 15%, a total of 71 patients in each arm are required, thus resulting in a total of 158 patients, including a 10% refusal rate. The data collected during the study could help improve the use of platelets during resuscitation management. If proven non-inferior in civilian settings, frozen platelets may be used in the future to optimize logistics and improve platelet availability in rural or remote areas for the treatment of (massive) bleeding trauma patients in civilian settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05502809. Registered on 16 August 2022.

Immunoassay for quantification of antigen-specific IgG fucosylation.

BACKGROUND: Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (FcγR). Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. Although afucosylated IgG can provide increased protection (malaria and HIV), it also boosts immunopathologies in alloimmune diseases, COVID-19 and dengue fever. Quantifying IgG fucosylation currently requires sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories. METHODS: Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). FINDINGS: IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R2=0.93, p < 0.0001). The FEASI method was then used to quantify IgG levels and fucosylation in COVID-19 convalescent plasma which was independently validated by LC-MS. INTERPRETATION: FEASI can be reliably implemented to measure relative and absolute IgG Fc fucosylation and quantify binding of antigen-specific IgG to FcγR in a high-throughput manner accessible to all diagnostic and research laboratories. FUNDING: This work was funded by the Stichting Sanquin Bloedvoorziening (PPOC 19-08 and SQI00041) and ZonMW 10430 01 201 0021.

Associations Between Symptoms, Donor Characteristics and IgG Antibody Response in 2082 COVID-19 Convalescent Plasma Donors.

Many studies already reported on the association between patient characteristics on the severity of COVID-19 disease outcome, but the relation with SARS-CoV-2 antibody levels is less clear. To investigate this in more detail, we performed a retrospective observational study in which we used the IgG antibody response from 11,118 longitudinal antibody measurements of 2,082 unique COVID convalescent plasma donors. COVID-19 symptoms and donor characteristics were obtained by a questionnaire. Antibody responses were modelled using a linear mixed-effects model. Our study confirms that the SARS-CoV-2 antibody response is associated with patient characteristics like body mass index and age. Antibody decay was faster in male than in female donors (average half-life of 62 versus 72 days). Most interestingly, we also found that three symptoms (headache, anosmia, nasal cold) were associated with lower peak IgG, while six other symptoms (dry cough, fatigue, diarrhoea, fever, dyspnoea, muscle weakness) were associated with higher IgG concentrations.

Dynamics of antibodies to SARS-CoV-2 in convalescent plasma donors.

OBJECTIVES: Characterisation of the human antibody response to SARS-CoV-2 infection is vital for serosurveillance purposes and for treatment options such as transfusion with convalescent plasma or immunoglobulin products derived from convalescent plasma. In this study, we longitudinally and quantitatively analysed antibody responses in RT-PCR-positive SARS-CoV-2 convalescent adults during the first 250 days after onset of symptoms. METHODS: We measured antibody responses to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the nucleocapsid protein in 844 longitudinal samples from 151 RT-PCR-positive SARS-CoV-2 convalescent adults. With a median of 5 (range 2-18) samples per individual, this allowed quantitative analysis of individual longitudinal antibody profiles. Kinetic profiles were analysed by mixed-effects modelling. RESULTS: All donors were seropositive at the first sampling moment, and only one donor seroreverted during follow-up analysis. Anti-RBD IgG and anti-nucleocapsid IgG levels declined with median half-lives of 62 and 59 days, respectively, 2-5 months after symptom onset, and several-fold variation in half-lives of individuals was observed. The rate of decline of antibody levels diminished during extended follow-up, which points towards long-term immunological memory. The magnitude of the anti-RBD IgG response correlated well with neutralisation capacity measured in a classic plaque reduction assay and in an in-house developed competitive assay. CONCLUSION: The result of this study gives valuable insight into the long-term longitudinal response of antibodies to SARS-CoV-2.

Pediatric resident knowledge of transfusion medicine: Results from the BEST-TEST3 international education needs assessment.

BACKGROUND: Transfusions are a common intervention within pediatrics and require unique considerations to optimize patient care. Poor knowledge of evidence-based transfusion practice can lead to misuse of transfusion therapy and harm. While there have been assessments of transfusion medicine knowledge of physicians caring for adult patients, there is little data regarding pediatricians. STUDY DESIGN AND METHODS: Using a published transfusion medicine knowledge exam for internal medicine physicians as a backbone, pediatric transfusion medicine experts, using an iterative process, developed a pediatric-specific examination. Pilot testing and Rasch analysis, a method used in high-stakes testing, was used to validate the exam. The exam and a previously validated survey on transfusion medicine training, attitudes, and perceived ability were administered to pediatric residents. Analysis consisted of descriptive statistics as well as comparisons of exam scores based on survey responses. RESULTS: 330 pediatric residents from 19 sites in 6 countries participated in the study. The vast majority (91%) of residents had obtained blood product consent. The mean exam score was 37.1% (range 9.5%-71.4%) with no statistical differences based on amount or perceived quality of transfusion medicine education or perceived ability. DISCUSSION: A rigorously validated exam has now been developed that can be used to assess pediatric transfusion medicine knowledge. A large international group of pediatric residents performed poorly on the exam demonstrating a pressing need for improved transfusion medicine education to ensure safe and appropriate administration of blood components to infants and children.

Prevalence of red-blood-cell and non-red-blood-cell-targeted autoantibodies in alloimmunized postpartum women.

BACKGROUND AND OBJECTIVES: Alloantibodies against red-blood-cell (RBC) antigens often coincide with alloantibodies against leucocytes and platelets and sometimes with autoantibodies towards various antigens. Chimerism may be one of the factors responsible for the combination of allo- and autoantibodies. Women with alloantibodies against RBC antigens causing haemolytic disease of the fetus and neonate may need to receive intrauterine transfusions. These transfusions increase not only maternal antibody formation but also fetomaternal bleeding and may enhance fetal chimerism. We determined the prevalence of and risk factors for autoantibodies against some common clinical target antigens, in alloimmunized women after IUT. MATERIALS AND METHODS: We tested for autoantibodies against RBC, anti-thyroid peroxidase, anti-extractable nuclear antigens, anti-cyclic citrullinated proteins and anti-tissue transglutaminase. Women with and without autoantibodies were compared for age; number of RBC alloantibodies, pregnancies and IUTs, and other factors that may play a role in immunization. RESULTS: Non-RBC-targeted autoantibodies were present in 40 of 258 tested women (15·5%, with 90% anti-TPO specificity), comparable to the prevalence reported in healthy Dutch women of these ages. Surprisingly, compared with women who had a single RBC alloantibody, a significantly higher proportion of women with multiple RBC alloantibodies had autoantibodies (5·3% and 18·4%, respectively; odds ratio 4·06, 95% CI: 1·20-13·7). Other characteristics of women with and without autoantibodies were not different. CONCLUSION: Multiple RBC alloantibodies after extensive allogeneic exposure during pregnancy and presumed increased fetomaternal chimerism are not associated with (selected) autoantibodies. Lack of allo-RBC multi-responsiveness seems associated with decreased auto(-TPO) antibody formation.

Association of Timing of Plasma Transfusion With Adverse Maternal Outcomes in Women With Persistent Postpartum Hemorrhage.

Importance: Early plasma transfusion for women with severe postpartum hemorrhage (PPH) is recommended to prevent coagulopathy. However, there is no comparative, quantitative evidence on the association of early plasma transfusion with maternal outcomes. Objective: To compare the incidence of adverse maternal outcomes among women who received plasma during the first 60 minutes of persistent PPH vs women who did not receive plasma for similarly severe persistent PPH. Design, Setting, and Participants: This multicenter cohort study used a consecutive sample of women with persistent PPH, defined as PPH refractory to first-line measures to control bleeding, between January 1, 2011, and January 1, 2013. Time-dependent propensity score matching was used to select women who received plasma during the first 60 minutes of persistent PPH and match each of them with a woman who had shown the same severity and received the same treatment of PPH but who had not received plasma at the moment of matching. Transfusions were not guided by coagulation tests. Statistical analysis was performed from June 2018 to June 2019. Exposures: Transfusion of plasma during the first 60 minutes of persistent PPH vs no or later plasma transfusion. Main Outcomes and Measures: Incidence of adverse maternal outcomes, defined as a composite of death, hysterectomy, or arterial embolization. Results: This study included 1216 women (mean [SD] age, 31.6 [5.0] years) with persistent PPH, of whom 932 (76.6%) delivered vaginally and 780 (64.1%) had PPH caused by uterine atony. Seven women (0.6%) died because of PPH, 62 women (5.1%) had a hysterectomy, and 159 women (13.1%) had arterial embolizations. Among women who received plasma during the first 60 minutes of persistent PPH, 114 women could be matched with a comparable woman who had not received plasma at the moment of matching. The incidence of adverse maternal outcomes was similar between the women, with adverse outcomes recorded in 24 women (21.2%) who received early plasma transfusion and 23 women (19.9%) who did not receive early plasma transfusion (odds ratio, 1.09; 95% CI, 0.57-2.09). Results of sensitivity analyses were comparable to the primary results. Conclusions and Relevance: In this cohort study, initiation of plasma transfusion during the first 60 minutes of persistent PPH was not associated with adverse maternal outcomes compared with no or later plasma transfusion, independent of severity of PPH.

HLA-matched platelet transfusions are effective only in refractory patients with positive HLA antibody screening.

BACKGROUND: Recipients of platelet transfusions with 1-hour corrected count increments (1hCCIs) of 7.5 or less on two subsequent platelet transfusions with random platelets may benefit from human leukocyte antigen (HLA)-matched platelet concentrates. We aimed to quantify the efficacy of HLA-matched platelets concentrates expressed in 1hCCIs. METHODS: We performed a cohort study among consecutive refractory patients who received HLA-matched platelet concentrates in the Netherlands between 1994 and 2017. We performed mixed-model linear regression comparing 1hCCIs after HLA split-antigen-matched transfusions with 1hCCIs after HLA-mismatched transfusions, adjusted for within-patient correlations. A donor-to-patient match was categorized as a split-match if all donor HLA-A and -B antigens were present in the patient as well; that is, donor and patient were HLA identical or compatible. Subgroup analyses were performed for patients with positive or negative HLA antibody screens. Finally, the additional effect of ABO mismatches on 1hCCIs was investigated. RESULTS: The 1hCCI after an HLA-matched transfusion was 14.09 (95% reference interval, 1.13-29.89). This was 1.94 (95% confidence interval [CI], 0.74-3.15) higher than 1hCCI after HLA-mismatched transfusions. In patients with negative HLA antibody screening tests, HLA matching did not affect 1hCCIs. Conditional on HLA matching, 1hCCIs decreased by 3.70 (95% CI, -5.22 to -2.18) with major ABO mismatches. CONCLUSION: Matched platelet concentrates yielded maximal 1hCCIs, whereas mismatched transfusions still resulted in adequate increments. There is no indication for HLA-matched platelets in patients with negative antibody screens.

Exposure to non-inherited maternal antigens by breastfeeding affects antibody responsiveness.

The observation, by Ray Owen and colleagues in 1954, that D-negative women were less likely to form anti-D antibodies against their D-positive fetus if their mother possessed the D-antigen, was not found in all later studies. We hypothesized that breastfeeding, received by the mother, may affect her immunity against non-inherited maternal red blood cell antigens. We studied a cohort of 125 grandmother-mother-child combinations, from a follow-up study of mothers after intrauterine transfusion of the fetus for alloimmune hemolytic disease. For mismatched red blood cell antigens the mother was exposed to, whether or not antibodies were formed, we determined whether her mother, the grandmother, carried these antigens. The duration for which the mothers were breastfed was estimated by way of a questionnaire. Using multivariate logistic regression analyses, the interaction term (non-inherited maternal antigen exposure by categorized breastfeeding period) showed that a longer breastfeeding period was associated with decreased alloimmunization against non-inherited maternal antigens (adjusted odds ratio 0.66; 95% confidence interval 0.48-0.93). Sensitivity analysis with dichotomized (shorter versus longer) breastfeeding periods showed that this lower risk was reached after two months (aOR 0.22; 95% CI 0.07-0.71) and longer duration of breastfeeding did not seem to provide additional protection. These data suggest that oral neonatal exposure to non-inherited maternal red blood cell antigens through breastfeeding for at least two months diminishes the risk of alloimmunization against these antigens when encountered later in life.

Consensus Recommendations for RBC Transfusion Practice in Critically Ill Children From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

OBJECTIVES: To date, there are no published guidelines to direct RBC transfusion decision-making specifically for critically ill children. We present the recommendations from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. DESIGN: Consensus conference series of multidisciplinary, international experts in RBC transfusion management of critically ill children. SETTING: Not applicable. INTERVENTION: None. SUBJECTS: Children with, or children at risk for, critical illness who receive or are at risk for receiving a RBC transfusion. METHODS: A panel of 38 content and four methodology experts met over the course of 2 years to develop evidence-based, and when evidence lacking, expert consensus-based recommendations regarding decision-making for RBC transfusion management and research priorities for transfusion in critically ill children. The experts focused on nine specific populations of critically ill children: general, respiratory failure, nonhemorrhagic shock, nonlife-threatening bleeding or hemorrhagic shock, acute brain injury, acquired/congenital heart disease, sickle cell/oncology/transplant, extracorporeal membrane oxygenation/ventricular assist/ renal replacement support, and alternative processing. Data to formulate evidence-based and expert consensus recommendations were selected based on searches of PubMed, EMBASE, and Cochrane Library from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. MEASUREMENTS AND RESULTS: The Transfusion and Anemia Expertise Initiative consensus conference developed and reached consensus on a total of 102 recommendations (57 clinical [20 evidence based, 37 expert consensus], 45 research recommendations). All final recommendations met agreement, defined a priori as greater than 80%. A decision tree to aid clinicians was created based on the clinical recommendations. CONCLUSIONS: The Transfusion and Anemia Expertise Initiative recommendations provide important clinical guidance and applicable tools to avoid unnecessary RBC transfusions. Research recommendations identify areas of focus for future investigation to improve outcomes and safety for RBC transfusion.

Recommendations on Selection and Processing of RBC Components for Pediatric Patients From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

OBJECTIVES: To present the recommendations and supporting literature for selection and processing of RBC products in critically ill children developed by the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. DESIGN: Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children METHODS:: The panel of 38 experts developed evidence-based, and when evidence was lacking, expert-based clinical recommendations as well as research priorities for RBC transfusions in critically ill children. The RBC processing subgroup included five experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. RESULTS: Five recommendations reached agreement (> 80%). Irradiated cellular products are recommended for children at risk of transfusion-associated graft versus host disease due to severe congenital or acquired causes of immune deficiency or when the blood donor is a blood relative. Washed cellular blood components and avoidance of other plasma-containing products are recommended for critically ill children with history of severe allergic reactions or anaphylaxis to blood transfusions, although patient factors appear to be important in the pathogenesis of reactions. For children with history of severe allergic transfusion reactions, evaluation for allergic stigmata prior to transfusion is recommended. In children with severe immunoglobulin A deficiency with evidence of antiimmunoglobulin A antibodies and/or a history of a severe transfusion reaction, immunoglobulin A-deficient blood components obtained either from an immunoglobulin A-deficient donor and/or washed cellular components is recommended. CONCLUSIONS: The Transfusion and Anemia Expertise Initiative consensus conference developed recommendations for selection and processing of RBC units for critically ill children. Recommendations in this area are largely based on pediatric and adult case report data.

An international investigation into O red blood cell unit administration in hospitals: the GRoup O Utilization Patterns (GROUP) study.

BACKGROUND: Transfusion of group O blood to non-O recipients, or transfusion of D- blood to D+ recipients, can result in shortages of group O or D- blood, respectively. This study investigated RBC utilization patterns at hospitals around the world and explored the context and policies that guide ABO blood group and D type selection practices. STUDY DESIGN AND METHODS: This was a retrospective study on transfusion data from the 2013 calendar year. This study included a survey component that asked about hospital RBC selection and transfusion practices and a data collection component where participants submitted information on RBC unit disposition including blood group and D type of unit and recipient. Units administered to recipients of unknown ABO or D group were excluded. RESULTS: Thirty-eight hospitals in 11 countries responded to the survey, 30 of which provided specific RBC unit disposition data. Overall, 11.1% (21,235/191,397) of group O units were transfused to non-O recipients; 22.6% (8777/38,911) of group O D- RBC units were transfused to O D+ recipients, and 43.2% (16,800/38,911) of group O D- RBC units were transfused to recipients that were not group O D-. Disposition of units and hospital transfusion policy varied within and across hospitals of different sizes, with transfusion of group O D- units to non-group O D- patients ranging from 0% to 33%. CONCLUSION: A significant proportion of group O and D- RBC units were transfused to compatible, nonidentical recipients, although the frequency of this practice varied across sites.

Trends in age and red blood cell donation habits among several racial/ethnic minority groups in the United States.

BACKGROUND: To meet the needs of a diverse patient population, an adequate supply of red blood cells (RBCs) from ethnic/racial minority donors is essential. We previously described the 10-year changes in minority blood donation in the United States. This study describes donation patterns by donor status, age, and race/ethnicity. STUDY DESIGN AND METHODS: Data on the age and the number of unique black/African American, Hispanic/Latino, Asian, and white RBC donors were obtained from eight US blood collectors for 2006, 2009, 2012, and 2015. Donors self-identified their race/ethnicity. First-time (FT) and repeat (R) donors were analyzed separately. RESULTS: Overall, for both FT and R donor groups, whites constituted the majority of unique donors (FT 66.7% and R 82.7%) and also donated the greatest proportion of RBC units (FT 66.6% and R 83.8%). Donors less than 20 years old comprised the greatest proportion of FT donors for all racial/ethnic groups (39.2%) and had the highest mean number of RBC donations per donor (1.12) among FT donors. Conversely, R donors less than 20 years old had some of the lowest mean number of RBC donations per donor (1.55) among R donors, whereas R donors at least 60 years old had the highest mean (1.88). Year by year, the percentage of FT donors who were less than 20 years old increased for all race/ethnicities. For R donors, whites were more frequently older, while Hispanics/Latinos and Asians were younger. CONCLUSIONS: Greater efforts to convert FT donors less than 20 years into R donors should be undertaken to ensure the continued diversity of the blood supply.

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.

Does a Platelet Transfusion Independently Affect Bleeding and Adverse Outcomes in Cardiac Surgery?

BACKGROUND: Conflicting results have been reported concerning the effect of platelet transfusion on several outcomes. The aim of this study was to assess the independent effect of a single early intraoperative platelet transfusion on bleeding and adverse outcomes in cardiac surgery patients. METHODS: For this observational study, 23,860 cardiac surgery patients were analyzed. Patients who received one early (shortly after cardiopulmonary bypass while still in the operating room) platelet transfusion, and no other transfusions, were defined as the intervention group. By matching the intervention group 1:3 to patients who received no early transfusion with most comparable propensity scores, the reference group was identified. RESULTS: The intervention group comprised 169 patients and the reference group 507. No difference between the groups was observed concerning reinterventions, thromboembolic complications, infections, organ failure, and mortality. However, patients in the intervention group experienced less blood loss and required vasoactive medication 139 of 169 (82%) versus 370 of 507 (74%; odds ratio, 1.65; 95% CI, 1.05 to 2.58), prolonged mechanical ventilation 92 of 169 (54%) versus 226 of 507 (45%; odds ratio, 1.47; 94% CI, 1.03 to 2.11), prolonged intensive care 95 of 169 (56%) versus 240 of 507 (46%; odds ratio, 1.49; 95% CI, 1.04 to 2.12), erythrocytes 75 of 169 (44%) versus 145 of 507 (34%; odds ratio, 1.55; 95% CI, 1.08 to 2.23), plasma 29 of 169 (17%) versus 23 of 507 (7.3%; odds ratio, 2.63; 95% CI, 1.50-4.63), and platelets 72 of 169 (43%) versus 25 of 507 (4.3%; odds ratio, 16.4; 95% CI, 9.3-28.9) more often compared to the reference group. CONCLUSIONS: In this retrospective analysis, cardiac surgery patients receiving platelet transfusion in the operating room experienced less blood loss and more often required vasoactive medication, prolonged ventilation, prolonged intensive care, and blood products postoperatively. However, early platelet transfusion was not associated with reinterventions, thromboembolic complications, infections, organ failure, or mortality.

The HLA-DRB1*15 phenotype is associated with multiple red blood cell and HLA antibody responsiveness.

BACKGROUND: Once a patient has produced a red blood cell (RBC) antibody, there is an increased risk of additional antibody formation after subsequent RBC exposure. Recently, we observed that HLA-DRB1*15 was overrepresented in 379 multiple RBC antibody responders compared to controls or 562 patients with a single RBC antibody (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3-2.3). In this study we evaluated whether the HLA-DRB1*15 represents a responder phenotype against HLA and/or RBC antigens. STUDY DESIGN AND METHODS: HLA-DRB1*15 frequencies in single and multiple antibody responders were compared between three groups of individuals: 1) those with HLA antibodies, 2) those with RBC antibodies, and 3) those with both RBC and HLA antibodies. RESULTS: A total of 3959 immunized patients (female-to-male ratio, 2.3) had been HLA-DRB1 typed. Among the 3275 individuals with HLA antibodies, the frequency of the DRB1*15 phenotype differed significantly from 19.7% in patients with a panel reactivity (PRA) of not more than 20% to 26.9% in patients with PRA of more than 80% (OR, 1.5; 95% CI, 1.2-1.9). This association between DRB1*15 and multiresponsiveness was mainly due to pregnancy-induced HLA immunization. In the 257 individuals with RBC and HLA antibodies, the frequency of DRB1*15 was 4.2 times (95% CI, 1.1-16) higher in those with multiple RBC antibodies and HLA-PRA of more than 50% compared to only single RBC responders with PRA of less than 20%. CONCLUSION: The HLA-DRB1*15 phenotype is associated with broad RBC and HLA immunization.

Transfusion reactions: prevention, diagnosis, and treatment.

Blood transfusion is one of the most common procedures in patients in hospital so it is imperative that clinicians are knowledgeable about appropriate blood product administration, as well as the signs, symptoms, and management of transfusion reactions. In this Review, we, an international panel, provide a synopsis of the pathophysiology, treatment, and management of each diagnostic category of transfusion reaction using evidence-based recommendations whenever available.