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Under the ISBT, the Working Party (WP) for Red Cell Immunogenetics and Blood Group Terminology is charged with ratifying blood group systems, antigens and alleles. This report presents the outcomes from four WP business meetings, one located in Basel in 2019 and three held as virtual meetings during the COVID-19 pandemic in 2020 and 2021.As in previous meetings, matters pertaining to blood group antigen nomenclature were discussed. New blood group systems and antigens were approved and named according to the serologic, genetic, biochemical and cell biological evidence presented.Seven new blood group systems, KANNO (defined numerically as ISBT 037), SID (038), CTL2 (039), PEL (040), MAM (041), EMM (042) and ABCC1 (043) were ratified. Two (039 and 043) were de novo discoveries, and the remainder comprised reported antigens where the causal genes were previously unknown. A further 15 blood group antigens were added to the existing blood group systems: MNS (002), RH (004), LU (005), DI (010), SC (013), GE (020), KN (022), JMH (026) and RHAG (030).The ISBT now recognizes 378 antigens, of which 345 are clustered within 43 blood group systems while 33 still have an unknown genetic basis. The ongoing discovery of new blood group systems and antigens underscores the diverse and complex biology of the red cell membrane. The WP continues to update the blood group antigen tables and the allele nomenclature tables. These can be found on the ISBT website (http://www.isbtweb.org/working-parties/red-cell-immunogenetics-and-blood-group-terminology/).

Brain metastasis still encompass very grim prognosis and therefore understanding the underlying mechanisms is an urgent need toward developing better therapeutic strategies. We uncover the intricate interactions between recruited innate immune cells and resident astrocytes in the brain metastatic niche that facilitate metastasis of melanoma and breast cancer. We show that granulocyte-derived lipocalin-2 (LCN2) induces inflammatory activation of astrocytes, leading to myeloid cell recruitment to the brain. LCN2 is central to inducing neuroinflammation as its genetic targeting or bone-marrow transplantation from LCN2-/- mice was sufficient to attenuate neuroinflammation and inhibit brain metastasis. Moreover, high LCN2 levels in patient blood and brain metastases in multiple cancer types were strongly associated with disease progression and poor survival. Our findings uncover a previously unknown mechanism, establishing a central role for the reciprocal interactions between granulocytes and astrocytes in promoting brain metastasis and implicate LCN2 as a prognostic marker and potential therapeutic target.

BACKGROUND In most centres, clinically significant percutaneous paravalvular leak (PVL) closure following valve replacement surgery is reserved for those considered high-risk for surgery. There is a paucity of data regarding the long-term outcomes of these patients. AIMS Our goals were to assess the long-term outcomes of patients undergoing percutaneous PVL closure. METHODS A total of 100 consecutive transcatheter PVL closure procedures (74 mitral, 26 aortic) were performed in 95 patients between February 2005 and August 2019 at our hospital. Data collected included procedural success rates, indication-specific outcomes and mortality. RESULTS Mean follow-up was 5.6±6.1 years, mean age 62.6±15.2 years, and 45.4% were female. The device was successfully implanted in 88 procedures (88.0%). Patients who presented with heart failure (n=57) had a significant improvement in NYHA classification (29.2% Class III/IV versus 100.0%, p

SARS-CoV-2 has been reported as a possible triggering factor for the development of several autoimmune diseases and inflammatory dysregulation. Here, we present a case report of a woman with a history of systemic lupus erythematosus and antiphospholipid syndrome, presenting with concurrent COVID-19 infection and immune thrombotic thrombocytopenic purpura (TTP). The patient was treated with plasma exchange, steroids, and caplacizumab with initial good response to therapy. The course of both TTP and COVID-19 disease was mild. However, after ADAMTS-13 activity was normalized, the patient experienced an early unexpected TTP relapse manifested by intravascular hemolysis with stable platelet counts requiring further treatment. Only 3 cases of COVID-19 associated TTP were reported in the literature thus far. We summarize the literature and suggest that COVID-19 could act as a trigger for TTP, with good outcomes if recognized and treated early.

The clinically important MAM blood group antigen is present on haematopoietic cells of all humans except rare MAM-negative individuals. Its molecular basis is unknown. By whole-exome sequencing we identify EMP3, encoding epithelial membrane protein 3 (EMP3), as a candidate gene, then demonstrate inactivating mutations in ten known MAM-negative individuals. We show that EMP3, a purported tumour suppressor in various solid tumours, is expressed in erythroid cells. Disruption of EMP3 by CRISPR/Cas9 gene editing in an immortalised human erythroid cell line (BEL-A2) abolishes MAM expression. We find EMP3 to associate with, and stabilise, CD44 in the plasma membrane. Furthermore, cultured erythroid progenitor cells from MAM-negative individuals show markedly increased proliferation and higher reticulocyte yields, suggesting an important regulatory role for EMP3 in erythropoiesis and control of cell production. Our data establish MAM as a new blood group system and demonstrate an interaction of EMP3 with the cell surface signalling molecule CD44., The molecular basis of the clinically important MAM blood group antigen present in most humans is unknown. We identify EMP3 as its encoding gene, establishing MAM as a new blood group system, and demonstrate the role of EMP3 in erythropoiesis through its interaction with the signalling molecule CD44.

Objective: To describe the experience with a multimodal therapeutic approach in a patient who developed toxic liver syndrome and fulminant hepatic failure following orthotopic liver transplantation (OLT) as a result of occlusion of the portal vein. Setting: Department of Intensive Care. Patient: A patient with liver cirrhosis secondary to autoimmune hepatitis and primary biliary cirrhosis who underwent orthotopic liver transplantation (OLT). Interventions: Transplant hepatectomy, plasmapheresis and retransplantation. Case Report: A 39-year-old man underwent an elective OLT. A routine postoperative doppler ultrasound examination a few hours after surgery revealed portal vein thrombosis. Attempts at recanalization failed, and the patient developed acute fulminant liver failure, which remained resistant to supportive therapy. A transplant hepatectomy was performed 9 hours later and plasmapheresis started. Following a 10-hour anhepatic period, the patient received a second liver, from an ABO-incompatible donor. The patient underwent column plasmapheresis and subsequent splenectomy to remove anti-B antibody to preserve the incompatible transplanted liver from immunogenic complications. The patient spent a total of 21 days in the Intensive Care Unit (ICU) before being discharged to a step-down ward. Conclusion: Our experience suggests that multimodal therapy, including transplant hepatectomy, plasmapheresis and retransplantation of an even non-ABO compatible liver may result in the successful outcome in patients with acute fulminant liver failure complicating OLT.

Patients with beta thalassemia major (TM) are transfusion-dependent (TD) since early childhood and for life. Development of alloantibodies and autoantibodies against red blood cell (RBC) antigens is increasingly recognized as a significant transfusion hazard, especially among heavily transfused patients. The aim of this study is to assess RBC alloimmunization and autoimmunization rates in TD TM patients treated in our Comprehensive Center of Adult Thalassemia, Hemoglobinopathies and Rare Anemias. TD TM patients, regularly transfused every 2-3 weeks, were included in the study. Clinical and RBC transfusion records, including RBC antibodies, since diagnosis in early childhood, were retrieved from patients' files and from the blood bank database. Forty TD TM patients, > 18 years of age, were included in the study. Alloimmunization was demonstrated in 17 (42.5%) patients. Thirty-four alloantibodies were detected, with the most frequent being RH related (12 of 34, 35.3%) followed by those of the Kell system (8 of 34, 23.5%). Age at first transfusion was positively related to the probability of developing alloantibodies (p = 0.02). Splenectomy was found to be correlated with developing alloantibodies (p = 0.016). Logistic regression analysis of the lifelong probability of developing alloantibodies on the age at first transfusion and splenectomy demonstrates a strong positive relationship (p = 0.002). A substantially high rate of alloimmunization was found among adult TD TM patients. Early initiation of RBC transfusions, avoidance of splenectomy and extended Rh and K antigen matching, can reduce the incidence of alloimmunization in TD TM patients.

Whole organ perfusion decellularization has been proposed as a promising method to generate non-immunogenic organs from allogeneic and xenogeneic donors. However, the ability to recellularize organ scaffolds with multiple patient-specific cells in a spatially controlled manner remains challenging. Here, we propose that replacing donor endothelial cells alone, while keeping the rest of the organ viable and functional, is more technically feasible, and may offer a significant shortcut in the efforts to engineer transplantable organs. Vascular decellularization was achieved ex vivo, under controlled machine perfusion conditions, in various rat and porcine organs, including the kidneys, liver, lungs, heart, aorta, hind limbs, and pancreas. In addition, vascular decellularization of selected organs was performed in situ, within the donor body, achieving better control over the perfusion process. Human placenta-derived endothelial progenitor cells (EPCs) were used as immunologically-acceptable human cells to repopulate the luminal surface of de-endothelialized aorta (in vitro), kidneys, lungs and hind limbs (ex vivo). This study provides evidence that artificially generating vascular chimerism is feasible and could potentially pave the way for crossing the immunological barrier to xenotransplantation, as well as reducing the immunological burden of allogeneic grafts.

Introduction: A restrictive transfusion strategy of packed red blood cells (PRBCs) has been associated with at least non-inferior patient outcomes in a variety of clinical settings. In December 2014, we conducted an educational intervention which consisted of an oral presentation and computerized notifications at a single tertiary medical center. Objective: The aim of this study was to examine the long-term effects of a simple and low-cost educational intervention aimed to promote awareness to transfusion guidelines. Methods: We retrospectively analyzed all PRBC transfusions ordered between 2014 and 2017. The primary end point was defined as the percentage of PRBC transfused to patients with hemoglobin (Hb) ≥8 g/dL. Results: Between 2014 and 2017, a total of 27,475 PRBCs were transfused in our medical center. There was a continuous reduction in the percentage of PRBCs transfused at a Hb level ≥8 g/dL between 2014 and 2017, with a matching increase in the PRBC percentage trans­fused at Hb Conclusion: A simple educational intervention likely contributed to sustained improvement in the appropriateness of PRBC transfusions.

Background: One of the main obstacles of providing home-based palliative care to transfusion-dependent hematology patients is the lack of home transfusions services. While healthcare professionals are concerned with safety and cost of home transfusions, the attitude of the patients toward home transfusions are mostly unknown. Aim: To obtain quantitative data regarding the willingness and concerns of transfusion-dependent patients with hematological diseases toward the option of home transfusions. Design: A cross sectional survey including a self-administered questionnaire in one of the three main spoken languages in Israel was administered to patients in 17 hospital hematology outpatient clinics between May 2019 and March 2020. Results: About 52% of 385 patients that participated in the survey preferred home transfusions to hospital transfusions. Gender, age, education, or type of disease were not associated with preference for home transfusions, nor were hospital location or its size. The likelihood to prefer home transfusions was significantly higher among the Hebrew-speakers and those who had not experienced adverse effects previously. The most significant factor associated with preference of home transfusions was a perceived negative effect of hospital-based transfusion on quality of life. The main reason to reject home transfusions was fear of possible adverse effects and concerns over losing contact with the medical staff at the treating hospital. Conclusion: These data suggest that a significant portion of transfusion-dependent patients in Israel view home transfusions as a preferred treatment option and that its successful implementation requires maintaining ongoing contact with the treating hospital.

Israel is currently struggling with the Coronavirus Disease (COVID-19) caused by SARS CoV-2. Transmission is increasing, with higher morbidity and mortality among populations at risk. Over-representation of blood type A was reported in COVID-19 patients with increased respiratory failure, while blood type O seems to have a protective effect. This may be caused by interference of anti-A antibodies in viral binding to the ACE receptor, different neutralization antibodies potency or variations in the stability of von Willebrand factor (VWF) multimers in different blood types. Since transfusion of convalescent COVID19 Plasma (CCP) is an accepted therapeutic modality, the Ministry of Health initiated a national project whereby CCP is collected by Magen David Adom (MDA) Blood Services using apheresis procedures and transfusions are approved by an experts committee, as part of the clinical trial or as compassionate treatment. Preliminary analysis of 49/170 patients treated so far shows improvement in 49%, with important relations with the anti-SARS-CoV-2 IgG antibodies level in the transfused plasma. Anti-SARS-CoV-2 antibodies were found in 83% of 1100 CCP donors, but a 13% decrease in antibodies level was detected in repeat donations. Blood type A was more predominant among CCP donors, when compared to MDA blood donors' data. A transfusion of CCP is a feasible and relatively safe therapeutic modality, mainly for patients with moderate COVID 19. CCP also serves as a source for the production of hyperimmune globulin for the treatment of COVID 19 and for passive immunization for populations at risk.

Hemolytic disease of the fetus and newborn (HDFN) is a severe form of anemia caused by maternal antibodies against fetal red blood cells (RBC) that can cause intrauterine and perinatal morbidity and mortality. The prevalence and specificities of alloantibodies among Israeli pregnant women and clinical outcomes for their fetuses and newborns are unknown. STUDY DESIGN AND METHODS A retrospective study of women who gave birth between January 1, 2011, and December 31, 2011, was performed. Data were obtained for obstetric admissions from 16 of 27 hospitals, which included results of maternal ABO, D, antibody screens, antibody identification, and requirements for intrauterine or newborn exchange transfusions. RESULTS Data on 90 948 women representing 70% of all births during 2011 were analyzed. Antibody screen was positive in 5245 (5.8%) women. Alloantibodies, excluding anti-D titer (

Introduction Extracorporeal photopheresis (ECP) serves as a second line treatment for patients with acute or chronic graft versus host disease (GVHD) and demonstrates efficacy in ameliorating GVHD in this setting. The mechanism by which ECP acts against GVHD has not been fully elucidated yet. Preliminary data point to an association between GVHD and increased neutrophil extracellular trap (NET) formation (NETosis) although much is unknown regarding the pathologic implication of this association. In this study we performed a preliminary assessment of the influence of ECP on NETosis among patients with GVHD. Methods Six patients after allogeneic transplantation treated with ECP for severe GVHD post allogeneic transplant at the Rabin Medical Center in Israel were enrolled to the study. Blood samples were obtained at 3 different time points: before an ECP cycle, immediately after the end of the ECP and 24h after the initiation of the ECP cycle. Neutrophils were obtained from whole blood samples using a percoll gradient. NETosis was assessed by measurement of neutrophil elastase activity using a commercial NETosis assay kit by Cayman Chemical and by immunofluorescence staining for DNA (DAPI (4',6-diamidino-2-phenylindole)) and for citrullinated H3 (H3Cit), a marker of NET formation. All assessments were executed in unstimulated neutrophils and in neutrophils that were stimulated with phorbol myristate acetate (PMA)(100nmol) for 4 hours. Results Six patients (4 males) with chronic GVHD were included in the study. The underlying hematologic disease was acute myeloid leukemia (AML) in four patients, B-cell acute lymphocytic leukemia (B-ALL) and myelodysplastic syndrome (MDS) each in one patient. ECP was executed for moderate to severe GVHD. We observed a sharp increase in the formation of NETs following treatment with ECP among all study participants. The level of neutrophil elastase activity was significantly elevated from a mean value of 2.21mU/mL (±0.6mU/mL) at baseline to a mean value of 13.82mU/mL (±5.54mU/mL) immediately after the treatment (p-value=0.0022). The mean level of neutrophil elastase activity was significantly elevated to a mean peak value of 17.35mU/mL (±10.74mU/mL) 24h following the initiation of the ECP cycle (p-value 0.0063 for the difference between the first and the last time points). Pre-incubation of the neutrophils with PMA yielded similar results, as the mean neutrophil elastase activity was 6.05mU/mL (±3.63mU/mL), 20.16mU/mL (±6.72mU/mL), and 24.57mU/mL (±13.59mU/mL) before the ECP cycle initiation, immediately after treatment, and 24h following ECP onset, respectively (Figure 1). In agreement, the expression of H3cit was also increased in neutrophils derived from patients with GVHD after ECP treatment (Figure 2). Conclusion Our preliminary data indicate that ECP induces NET formation among patients with GVHD. NETosis might play a role in the therapeutic effects of ECP in this setting. These initial results might set the stage for future studies in this field. Figure 1 Figure 1. Disclosures Goldberg: MSD Israel: Consultancy. Yeshurun: Astellas: Consultancy; Janssen: Consultancy. Wolach: Janssen: Consultancy; Abbvie: Consultancy, Honoraria, Research Funding; Astellas: Consultancy; Amgen: Research Funding; Novartis: Consultancy; Neopharm: Consultancy.

BACKGROUND Hospital transfusion committees (HTCs) can oversee all aspects of transfusion practice at a hospital. This survey sought to identify which quality variables were being reported at HTCs around the world. STUDY DESIGN AND METHODS A working party composed of members of the Biomedical Excellence for Safer Transfusion (BEST) collaborative developed a survey of quality variables that could be potentially presented at HTC meetings. The survey was electronically sent to all BEST members who were encouraged to complete it if they were active on an HTC and to send it to other colleagues with similar experience. An expert panel was convened to determine which quality variables are the most important for review at HTC meetings. RESULTS There were 121 respondents; the majority were from Europe (52%), Asia (19%), or North America (19%). Most respondents (68%) were at university hospitals. Of the 117 (97%) respondents with an HTC, the committee most often met quarterly (42%) and reviewed transfusion reactions (79%) and risk management–reported events (52%). The HTCs most commonly included transfusion medicine physicians, anesthesiologists, and other physicians who regularly transfuse blood products. Some of the most commonly reported quality variables included number of blood products transfused, wasted, and expired and the number of improperly labeled specimens. The expert panel analysis revealed that some variables that were deemed important were not being frequently reported at HTCs. CONCLUSION There is variability in the variables being reported at HTCs around the world with some important variables not frequently reported.

Patients with beta thalassemia major (TM) are transfusion-dependent (TD) since early childhood and for life. Development of alloantibodies and autoantibodies against red blood cell (RBC) antigens is increasingly recognized as a significant transfusion hazard, especially among heavily transfused patients. The aim of this study is to assess RBC alloimmunization and autoimmunization rates in TD TM patients treated in our Comprehensive Center of Adult Thalassemia, Hemoglobinopathies and Rare Anemias. TD TM patients, regularly transfused every 2-3 weeks, were included in the study. Clinical and RBC transfusion records, including RBC antibodies, since diagnosis in early childhood, were retrieved from patients' files and from the blood bank database. Forty TD TM patients,18 years of age, were included in the study. Alloimmunization was demonstrated in 17 (42.5%) patients. Thirty-four alloantibodies were detected, with the most frequent being RH related (12 of 34, 35.3%) followed by those of the Kell system (8 of 34, 23.5%). Age at first transfusion was positively related to the probability of developing alloantibodies (p = 0.02). Splenectomy was found to be correlated with developing alloantibodies (p = 0.016). Logistic regression analysis of the lifelong probability of developing alloantibodies on the age at first transfusion and splenectomy demonstrates a strong positive relationship (p = 0.002). A substantially high rate of alloimmunization was found among adult TD TM patients. Early initiation of RBC transfusions, avoidance of splenectomy and extended Rh and K antigen matching, can reduce the incidence of alloimmunization in TD TM patients.

Introduction: Patients treated with direct Xa inhibitors may require urgent surgery. Administration of prothrombin complex concentrate (PCC) in this setting is common; however, it is based on limited experience in healthy volunteers. Objective: To characterize the population receiving PCC for apixaban/rivaroxaban reversal prior to an urgent surgery and evaluate its efficacy and safety. Methods: This was a retrospective study in 2 tertiary hospitals. Bleeding was evaluated based on surgical reports, hemoglobin drop, and the use of blood products or additional PCC during 48 h. Safety measures were thrombotic complications and 30-day mortality. Results: Sixty-two patients aged 80.7 ± 9 years, treated with apixaban (39.63%) or rivaroxaban (23.37%), received PCC before an urgent surgery/procedure. Most underwent abdominal operation (61%), orthopedic surgery (13%), or transhepatic cholecystostomy insertion (10%). Bleeding during surgery was reported in 3 patients (5%), no patient required additional PCC, and 16 patients (26%) received packed cells (median: 1 unit, range: 1–5). The 30-day mortality and thrombosis rates were 21% (n = 13) and 3% (n = 2), respectively. The cause of death was related to the primary disease, most commonly sepsis. No patient died due to bleeding/thrombosis. Conclusions: Our results support the use of PCC to achieve hemostasis in patients treated with Xa inhibitors prior to an urgent surgery.

The Working Party has met twice since the last report: in Seoul, South Korea 2014, and in London, UK 2015, both in association with the International Society of Blood Transfusion (ISBT) Congress. As in previous meetings, matters pertaining to blood group antigen nomenclature were discussed. Eleven new blood group antigens were added to seven blood group systems. This brings the current total of blood group antigens recognized by the ISBT to 346, of which 308 are clustered within 36 blood groups systems. The remaining 38 antigens are currently unassigned to a known blood group system.

BACKGROUND As patient blood management becomes more widespread, fewer red blood cell (RBC) units have been transfused. This multinational study evaluated changes in blood center RBC distributions. STUDY DESIGN AND METHODS Data on number and ABO and D groups of RBC distributions were obtained from several large American blood centers and national or provincial blood services (NPBS) from fiscal year (FY) 2010 through FY2014. Due to relatively larger numbers of distributions and differences in ABO and D groups between the Japanese Red Cross and the other NPBS, Japanese data were not included in distributions calculations. RESULTS Data from seven American blood centers and eight NPBS were obtained. Overall, at both the American and the seven NPBS that were analyzed, there were declines in the number of RBC distributions between FY2010 and FY2014, 16.9 and 8.0%, respectively. The number of O– RBC distributions decreased by 9.0% at American blood centers but the proportion of RBC distributions that were O– increased by 9.3% during this time. The NPBS had 1.6% increase in O– RBC distributions and 10.5% increase in the proportion of O– distributions. The proportion of O+ distributions increased slightly over time at American centers (2.9%) while decreasing slightly (1.1%) at NPBS despite reductions in the absolute numbers of O+ distributions. Overall there was 2.6% decrease in the proportion of B+ and AB+ RBCs distributed and 13.6% absolute reduction in the number of these units distributed. CONCLUSION Although overall RBC distributions have decreased over time, the proportion of O units has increased substantially.

International rare blood donor panels or registries are important in the consistent availability of rare blood for patients who need this scarce resource. In countries where it has been possible to commit resources to this effort and often where the need is great, donors have been entered into a registry. The ISBT leadership recognized the importance of this very challenging inventory management activity and created a Working Party to support it. Individual countries support the WHO International Rare Donor Panel by submitting their donors' phenotype or genotype information to be catalogued into the database. It is extremely important that this database be cultivated and grown. The contributing countries keep their list updated and supply the blood product as they can when requested. It is known that some blood types are extremely scarce worldwide and requests for these are particularly difficult to fulfil. Thus, it is important to have a protocol to identify and recruit donors with rare blood types. It is equally or perhaps more important to ensure that the patients who need the rare blood are being managed appropriately in the presence and absence of rare blood products being available.

CD55 (complement decay-accelerating factor) inhibits the alternative and classical arms of the complement pathway. Three patients with protein-losing enteropathy and a genetic variant predicted to result in loss of function of CD55 had a response to eculizumab.

Background and objectives: The International Society of Blood Transfusion (ISBT) Working Party for Red Cell Immunogenetics and Blood Group Terminology meets in association with the ISBT congress and has met three times since the last report: at the international meetings held in Dubai, United Arab Emirates, September 2016 and Toronto, Canada, June 2018; and at a regional congress in Copenhagen, Denmark, June 2017 for an interim session. Methods: As in previous meetings, matters pertaining to blood group antigen nomenclature and classification were discussed. New blood group antigens were approved and named according to the serologic and molecular evidence presented. Results and conclusions: Fifteen new blood group antigens were added to eight blood group systems. One antigen was made obsolete based on additional data. Consequently, the current total of blood group antigens recognized by the ISBT is 360, of which 322 are clustered within 36 blood groups systems. The remaining 38 antigens are currently unassigned to a known system. Clinically significant blood group antigens continue to be discovered, through serology/sequencing and/or recombinant or genomic technologies.

BACKGROUND AnWj is a high-incidence blood group antigen associated with three clinical disorders: lymphoid malignancies, immunologic disorders, and autoimmune hemolytic anemia. The aim of this study was to determine the genetic basis of an inherited AnWj-negative phenotype. METHODS We identified a consanguineous family with two AnWj-negative siblings and 4 additional AnWj-negative individuals without known familial relationship to the index family. We performed exome sequencing in search for rare homozygous variants shared by the two AnWj-negative siblings of the index family and searched for these variants in the four non-related AnWj-negative individuals. RESULTS Exome sequencing revealed seven candidate genes that showed complete segregation in the index family and for which the two AnWj-negative siblings were homozygous. However, the four additional non-related AnWj-negative subjects were homozygous for only one of these variants, rs114851602 (R320Q) in the SMYD1 gene. Considering the frequency of the minor allele, the chance of randomly finding 4 consecutive such individuals is 2.56 × 10-18 . CONCLUSION We present genetic and statistical evidence that the R320Q substitution in SMYD1 underlies an inherited form of the AnWj-negative blood group phenotype. The mechanism by which the mutation leads to this phenotype remains to be determined.

Haemolytic transfusion reactions (HTRs) may be immediate/acute (AHTR) usually due to immune ABO incompatibility or delayed (DHTR) seen days to weeks following transfusion and caused by an anamnestic immune response to red cell antigens (Kidd, Rh, Duffy and others). AHTR may cause severe morbidity and mortality even if recognized early. Presently, there is no therapy that can reliably treat the effects of acute haemolysis. Therefore, RBC (and other blood components) should be transfused only if clinically indicated. Strict adherence to guidelines and SOP's is essential for prevention of this avoidable severe complication. Awareness, close observation of patients receiving transfusion, early recognition of a transfusion reaction, prompt cessation of transfusion and appropriate supportive care are essential to minimize morbidity and mortality. Factors influencing the outcome of HTRs include antibody and antigen characteristics as well as patient age and comorbidities. DHTRs are more frequent in patients with sickle cell disease (SCD), thalassaemia and haematological conditions such as autoimmune haemolytic anaemia (AIHA) and myelodysplastic syndromes (MDS). In these patients, distinction between haemolysis caused by alloantibodies or autoantibodies is challenging, especially if hyperhaemolysis is present. Investigation of HTRs should include all aspects of the transfusion chain – administrative, clinical and laboratory. In patients in whom the blood bank laboratory cannot identify a cause for haemolysis, other causes for immune and nonimmune haemolysis should be sought. New insights into the pathogenesis of haemolysis might aid in developing novel therapies for amelioration and treatment of HTRs. Nonetheless, prevention of HTRs should be the major goal.

Many premature and full-term newborns receive prophylactic platelet transfusions to prevent bleeding, particularly the most prevalent one, i.e, intracranial hemorrhages. However, the platelet count threshold above which bleeding is prevented and the efficacy of platelet transfusion in thrombocytopenic neonates, have yet to be established. Therefore, inter-Neonatal Intensive Care Units (NICU) variations in treatment indications and practices are expected. Considerable inter-NICU variations will emphasize the need for guidelines on platelet transfusions to neonates and premature infants.To examine platelet products selection and indications for transfusion among neonatologists in Israel. Research and Methods: Electronic questionnaires addressing the choice of platelet products and the platelet count threshold for transfusion in various clinical settings were sent to 25 neonatal units.All 25 neonatal units responded (100% response rate). There was considerable variation in product selection among the different neonatal units. Up to 24% of the participating units reported selecting nontraditional products. Variation was also found in thresholds for platelet transfusion - several units used high thresholds while others used low ones. Traditional guidelines were followed in up to 64% of cases in selected clinical scenarios.There is considerable variation in both platelet product selection and platelet count thresholds for transfusion among the different neonatal units.A low threshold for platelet transfusion increases the risk for bleeding, whereas a high threshold increases the prevalence of complications from transfusion of blood products. Adherence to guidelines may prevent both such sequelae. Summary: Such variation in platelet transfusion among neonatologists emphasizes the need for an accepted policy. We recommend setting up a committee of neonatologists, pediatric hematologists and blood service experts which aims to establish an appropriate policy regarding the prevention of platelet transfusion sequelae in newborns.

The International Society of Blood Transfusion Working Party on red cell immuno-genetics and blood group terminology convened during the International congress in Cancun, July 2012. This report details the newly identified antigens in existing blood group systems and presents three new blood group systems.

Transfusion support of patients with antibodies against high frequency (HF) antigens or a combination of antibodies that is rare is challenging and requires multidisciplinary cooperation. The treating physician should decide if there is a definitive clinical need for red blood cell (RBC) transfusion for the specific patient. According to recent clinical trials RBC transfusion is usually not indicated if the patient is haemodynamically stable and the haemoglobin (Hb) is higher than 7 g/dl. Alternative strategies for patient support might be required if rare blood is unavailable or while awaiting rare RBC unit arrival from national or international sources.

Hospital transfusion committees (HTCs) can oversee all aspects of transfusion practice at a hospital. This survey sought to identify which quality variables were being reported at HTCs around the world.A working party composed of members of the Biomedical Excellence for Safer Transfusion (BEST) collaborative developed a survey of quality variables that could be potentially presented at HTC meetings. The survey was electronically sent to all BEST members who were encouraged to complete it if they were active on an HTC and to send it to other colleagues with similar experience. An expert panel was convened to determine which quality variables are the most important for review at HTC meetings.There were 121 respondents; the majority were from Europe (52%), Asia (19%), or North America (19%). Most respondents (68%) were at university hospitals. Of the 117 (97%) respondents with an HTC, the committee most often met quarterly (42%) and reviewed transfusion reactions (79%) and risk management-reported events (52%). The HTCs most commonly included transfusion medicine physicians, anesthesiologists, and other physicians who regularly transfuse blood products. Some of the most commonly reported quality variables included number of blood products transfused, wasted, and expired and the number of improperly labeled specimens. The expert panel analysis revealed that some variables that were deemed important were not being frequently reported at HTCs.There is variability in the variables being reported at HTCs around the world with some important variables not frequently reported.

As patient blood management becomes more widespread, fewer red blood cell (RBC) units have been transfused. This multinational study evaluated changes in blood center RBC distributions.Data on number and ABO and D groups of RBC distributions were obtained from several large American blood centers and national or provincial blood services (NPBS) from fiscal year (FY) 2010 through FY2014. Due to relatively larger numbers of distributions and differences in ABO and D groups between the Japanese Red Cross and the other NPBS, Japanese data were not included in distributions calculations.Data from seven American blood centers and eight NPBS were obtained. Overall, at both the American and the seven NPBS that were analyzed, there were declines in the number of RBC distributions between FY2010 and FY2014, 16.9 and 8.0%, respectively. The number of O- RBC distributions decreased by 9.0% at American blood centers but the proportion of RBC distributions that were O- increased by 9.3% during this time. The NPBS had 1.6% increase in O- RBC distributions and 10.5% increase in the proportion of O- distributions. The proportion of O+ distributions increased slightly over time at American centers (2.9%) while decreasing slightly (1.1%) at NPBS despite reductions in the absolute numbers of O+ distributions. Overall there was 2.6% decrease in the proportion of B+ and AB+ RBCs distributed and 13.6% absolute reduction in the number of these units distributed.Although overall RBC distributions have decreased over time, the proportion of O units has increased substantially.

BACKGROUND: Fetal neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder in the fetus or neonate caused by maternal alloantibodies directed against fetal platelet (PLT) antigens inherited from the father. The immune-dominant antigen leading to severe FNAIT is the human PLT antigen (HPA)-1, whose polymorphism constitutes an epitope for human leukocyte antigens (HLAs), usually DRB3*0101 leading to an immune response. STUDY DESIGN AND METHODS: In this study our aims were to find whether other allele variants of the β subunit of the HLA-DR family specifically focused on the HLA residues that bind Position 33 of the HPA-1 integrin contribute to FNAIT development and affect response to treatment and whether coexistence of both anti-HPA-1a and anti-HLA Class I specific against the father's antigens leads to a more severe thrombocytopenia in the newborn. We examine the genotype of 23 mothers to newborns with FNAIT compared to a control group. RESULTS: Our results suggested that, when HPA-1 incompatibility with the husband is found, the presence of two HLA alleles (DRB3*01:01 and DRB4*01:01) in the mother increases the risk and severity of FNAIT and reduces the success of a preventive immunoglobulin G treatment. We provide a structural model for the molecular basis of the rational effects of the different HLA alleles. In addition, we found that the presence of both anti-HPA-1 and anti-HLAs did not aggravate FNAIT in comparison to mothers harboring only anti-HPA-1. CONCLUSION: Overall, we suggest that a specific genotyping of the mother in relation to HLA-DRB as well as HPA-1 can serve as an antenatal diagnostic tool, particularly in siblings of women who gave birth to neonates with FNAIT.

BACKGROUND: The quality of blood components prepared from whole blood (WB) units rapidly cooled to 20 to 24°C and stored for prolonged periods using butane-1,4-diol “cooling plates,” and the factors that determine the functional activity of these cooling systems under various temperature conditions were investigated. STUDY DESIGN AND METHODS: Validation of the cooling systems functions, performed in different environmental temperature-time schemes using WB-mock units, were recorded and analyzed in 106 temperature curves, simulating environmental conditions of blood storage at the blood drives and transport to the blood services component laboratory. The quality of red blood cells, fresh-frozen plasma, platelet concentrates, and cryoprecipitate units was studied on components routinely prepared in 2007 to 2009 from WB units collected in citrate-phosphate-dextrose-adenine or citrate-phosphate-dextrose (CPD), rapidly cooled, and stored in ambient temperature for up to 22 hours postdonation using the cooling systems. RESULTS: Quality variables of blood components prepared from WB units rapidly cooled and held overnight for up to 22 hours postcollection, using both cooling systems, met the allowed ranges of American, European, and Israeli standards. Temperature validation of the cooling systems resulted in national standard operating procedures for the proper use in different ambient temperature ranges. CONCLUSION: The rapid cooling of WB and prolonged storage under different environmental conditions using cooling plate systems enabled standardization of blood storage at and transportation from all collection sites. It provided an efficient, reproducible, and cost-effective way to ensure good quality blood components, while utilizing more efficient logistic and administrative means.

Introduction: Patients treated with direct Xa inhibitors may require an urgent surgery. A reversal agent for Xa inhibitors was recently approved for major bleeding but not prior to urgent surgery. Administration of prothrombin complex concentrate (PCC) in this setting is a common practice; however, it is based on limited experience in healthy volunteers. Objective: To characterize the population receiving PCC for apixaban/rivaroxaban reversal prior to an urgent surgery/procecdure and evaluate its efficacy and safety. Methods: A retrospective study in two tertiary hospitals. Bleeding was evaluated by surgical reports, hemoglobin drop and use of packed red blood cells or additional PCC during 48h. Safety measures were thrombotic complications and 30-day mortality. Results: Sixty-two patients, aged 80.7±9, received PCC prior to urgent invasive procedures ;39 (63%) received apixaban and 23( 37%) rivaroxaban. Ninety percent of them received anticoagulation due to atrial fibrillation. Most urgent procedures were abdominal surgery (61%), orthopedic surgery (13%) or transhepatic cholecystostomy insertion (10%). Mean dose of PCC was 26.6±8 U/kg. Fourteen patients (23%) received 1 gram of tranexamic acid. Bleeding was reported by surgeons in 3(5%) patients and no patient required additional PCC. Sixteen (26%) patients received packed cells (median 1 unit, range 1-5). Thirty day mortality and thrombosis were 13(21%) and 2(3%) respectively. Cause of death was related to the primary disease or sepsis. No patient died due to bleeding/thrombosis. Conclusions: PCC is safe and effective for the reversal of Xa inhibitors prior to an urgent surgery/procedure. Disclosures No relevant conflicts of interest to declare.

SUMMARY: BACKGROUND: Major surgery and severe trauma typically lead to massive blood loss requiring rapid transfusion of large amounts of blood products. It has been suggested that fresh, unrefrigerated whole blood provides a haemostatic advantage in this setting. The aim of the current study was to compare the clot formation parameters of fresh, unrefrigerated whole blood and whole blood reconstituted from components stored for varying periods of time, using rotational thromboelastography (ROTEM®). METHODS: Fresh whole blood and reconstituted whole blood using combinations of non-leucoreduced red cell units (stored for 7, 14, 21, 28, or 35 days), platelet concentrates (stored for 1, 3 or 5 days), and fresh frozen plasma (stored for 6 months) were analysed using ROTEM. Measurements of the clotting time (CT), clot formation time (CFT), and maximal clot firmness (MCF) were compared between units of fresh whole blood and reconstituted whole blood samples. RESULTS: There was no difference in the haemostatic parameters measured of fresh whole blood and reconstituted whole blood using red cell units stored for less than 21 days. ROTEM demonstrated that the CT and CFT were significantly shorter for reconstituted whole blood samples using red cells stored for longer than 21 days when compared to fresh whole blood and to reconstituted whole blood samples using red cell units stored for less than 21 days. The CT was inversely correlated to the duration of platelet storage. The MCF was unchanged regardless of duration of blood product storage. CONCLUSION: Fresh unrefrigerated whole blood and blood products stored for short duration (less than 21 days) were not superior to those stored for longer durations.