Severe Hemolytic Transfusion Reaction Research Articles

Integrated analyses reveal unexpected complex inversion and recombination in RH genes

AbstractPhenotype D-- is associated with severe hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. It is typically caused by defective RHCE genes. In this study, we identified a D-- phenotype proband and verified Rh phenotypes of other 6 family members. However, inconsistent results between the phenotypic analysis and Sanger sequencing revealed intact RHCE exons with no mutations in the D-- proband, but the protein was not expressed. Subsequent whole-genome sequencing by Oxford Nanopore Technologies of the proband revealed an inversion with ambiguous breakpoints in intron 2 and intron 7 and copy number variation loss in the RHCE gene region. Given that the RHCE gene is highly homologous to the RHD gene, we conducted a comprehensive analysis using Pacific Biosciences long-read target sequencing, Bionano optical genome mapping, and targeted next-generation sequencing. Our findings revealed that the proband had 2 novel recombinant RHCE haplotypes, RHCE∗Ce(1-2)-D(3-10) and RHCE∗Ce(1-2)-D(3-10)-Ce(10-8)-Ce(3-10), with clear-cut breakpoints identified. Furthermore, the RH haplotypes of the family members were identified and verified. In summary, we made, to our knowledge, a novel discovery of hereditary large inversion and recombination events occurring between the RHD and RHCE genes, leading to a lack of RhCE expression. This highlights the advantages of using integrated genetic analyses and also provides new insights into RH genotyping.

Discrepancy in ABO Blood Grouping: A Report of B Subgroup with Cold Alloantibody

The ABO antigens are the most important in both blood transfusion and transplantation as their antibody can cause severe haemolytic transfusion reaction when ABO-incompatible transfusion occurs. It has been claimed that variants of the ABO blood group are very rare, including B subgroups. We reported a young healthy female with B subgroup and underlying cold-reacting alloantibody causing challenges in determining of her ABO blood group. Initial ABO blood grouping was misinterpreted as group O. Presence of alloantibody in her plasma was suspected after revealing positive antibody screening. Repeated blood grouping at 37oC revealed a discrepancy of the forward and reverse grouping, which suggested B subgroup. Cross-matching showed difficulties in finding compatible blood with both group O and B cells due to the presence of clinically significant cold alloantibody. Determining of correct ABO blood group is mandatory in transfusion practices as haemolytic transfusion reaction can be prevented.

Treatment with plasma exchange of a pregnant woman with anti-PP1Pk alloimmunization: A case report

The histo-blood group antigens P, P1 and Pk are a closely related set of glycosphingolipid structures expressed by red blood cells and other tissues. None of these three characters is expressed on p cells, a null phenotype that arises in the context of homozygous mutation of the A4GALT gene. Subjects with p phenotype spontaneously develop a natural alloantibody named anti-PP1Pk, which is a mixture of IgG and IgM against P1, P and Pk. While anti-P1 is a weak cold antibody with poor clinical significance, anti-P and anti-Pk antibodies are potent haemolysins responsible for severe hemolytic transfusion reactions. The rare anti-PP1Pk alloantibodies are associated with recurrent spontaneous abortion in the first trimester of gestation. P and Pk antigens are expressed at high levels on the placenta and antibodies directed against both these structures are deleterious to placental trophoblasts. Here we describe the use of plasma exchange (PEX) in a nulliparous 39-year-old woman with anti-PP1Pk antibodies and a history of repeated spontaneous early abortions and hypofertility. The patient underwent apheresis starting from the third week throughout the pregnancy and a healthy child was delivered by cesarean section at 35 WG. The newborn required only phototherapy within a few days of life. We can state that an early treatment with the only PEX has proven to be effective and safe in the management of a fetomaternal P-incompatibility caused by a high anti-PP1Pk titer (256).

Comparison of the conventional tube and erythrocyte-magnetized technology in titration of red blood cell alloantibodies

Erythrocyte alloantibodies are mainly produced after immune stimulation, such as blood transfusion, pregnancy, and transplantation, and are the leading causes of severe hemolytic transfusion reactions and difficulty in blood grouping and matching. Therefore, antibody screening is critical to prevent and improve red cell alloantibodies. Routine tube assay is the primary detection method of antibody screening. Recently, erythrocyte-magnetized technology (EMT) has been increasingly used in clinical practice. This study intends to probe the application and efficacy of the conventional tube and EMT in red blood cell alloantibody titration to provide a reference for clinical blood transfusion. To investigate the application value of conventional tube and EMT in red blood cell alloantibody titration and enhance the safety of blood transfusion practice. A total of 1298 blood samples were harvested from blood donors at the Department of Blood Transfusion of our hospital from March 2021 to December 2022. A 5 mL blood sample was collected in tubing, which was then cut, and the whole blood was put into a test tube for centrifugation to separate the serum. Different red blood cell blood group antibody titers were simultaneously detected using the tube polybrene test, tube antiglobulin test (AGT), and EMT screening irregular antibody methods to determine the best test method. Simultaneous detection was performed through the tube polybrene test, tube AGT and EMT screening irregular antibodies. It was discovered that the EMT screening irregular antibody method could detect all immunoglobulin G (IgG) and immunoglobulin M (IgM) irregular antibodies, and the results of manual tube AGT were satisfactory, but the operation time was lengthy, and the equipment had a large footprint. The EMT screening irregular antibody assay was also conducted to determine its activity against type O Rh (D) red blood cells, and the outcomes were satisfactory. Furthermore, compared to the conventional tube method, the EMT screening irregular antibody method was more cost-effective and had significantly higher detection efficiency. With a higher detection rate, the EMT screening irregular antibody method can detect both IgG and IgM irregular antibodies faster and more effectively than the conventional tube method.

Management of a rare red cell antibody in pregnancy

Vel is a clinically significant, high incidence blood group antigen. Alloimmunisation of the rare Vel-negative individual (1:4000) with Vel-positive red cells results in the development of anti-Vel antibodies that are associated with severe haemolytic transfusion reactions on re-exposure to Vel-positive blood, necessitating transfusion with exceedingly limited supplies of Vel-negative red cells. We describe a case of patient blood management in a 35-year-old pregnant woman with anti-Vel antibodies and risk for post-partum haemorrhage (PPH). Confirmatory testing for anti-Vel was performed by Lifeblood. There was only one known compatible donor identified in Australia with a very limited inventory of cryopreserved red cells. As the patient was pregnant, autologous collection was not possible. Due to these limitations in supply of Vel-negative red cells, a multifaceted alternative care plan was developed, including: (1) Patient optimisation for delivery, including replacement of haematinic factors; (2) Early anaesthetic and obstetrics involvement was sought in planning delivery; (3) In the event of PPH, a clearly documented prescription of haemostatic products was suggested including upfront cryoprecipitate, platelets, FFP, tranexamic acid, and recombinant Factor VIIa. Fortunately, the patient had an uncomplicated delivery. This case demonstrates the importance of a comprehensive transfusion plan for patients with rare blood groups.

Blood Groups ABO and Rh System Among Paternity and Kinship Cases of Iraqi Medical Legal Directorate

ABO and Rh are the most important blood group systems with various distributions reported for different populations. Traditional ABO blood group and Rh serology is based on the immunoreactivity of antisera with the carbohydrate A, B and H antigens on Red Blood Cells (RBC). Due to its medical importance in relation to different diseases, pursuing a line of investigation on the ABO and Rh blood group systems has been of significance for years. It is well known that these blood group systems are of great importance in blood transfusion and organ transplantation. Furthermore, the susceptibility to several diseases has been associated with the ABO phenotype, but such correlation remains controversial. Progress in the molecular biology of the ABO system has recognized the molecular basis of the red blood cell antigens and has provided a genetic model for ABO polymorphism at the molecular level. The ABH antigens are not primary gene product, but they are the enzymatic reaction product of enzymes called glycosyltransferases. After the ABO system, the Rh (Rhesus) blood group system is regarded as the second most important blood group system, as some of the severe hemolytic transfusion reactions and most hemolytic disease of the fetus and new born (HDFN) cases are associated with antibodies to the Rh group antigens. Objectives: To determine ABO blood group and Rh factor phenotype antigens frequency, distribution, and document among paternity cases of Iraqi Medical Legal Directorate / Clinical Forensic Department / paternity and kinship division. Materials and Methods: The material and methods were used ABO and Rh kits for detection phenotype antigens of this blood types, the principle of test is one step immunological reaction. Total samples (1997) were referred to medical Legal Directorate (MLD). Out of the total participants there were 1815 (98.4%) of samples complete information for inclusion criteria. the sample were used for estimation of phenotypic distribution of ABO, Rh. ABO blood group serology was performed at MLD, Paternity and Kinship Division using commercially available monoclonal Anti-A, Anti-B, reagents according to the national blood bank standard operating procedures. The Method principle is based on antigen antibody reaction (agglutination) some tests were confirmed under microscope examination to see weak reaction. Results: The most common blood group was O (52.3%) and the least common was AB (3.18%).97.7% of the blood participants were Rh Positive and the rest were Rh Negative. Most participants were young adults, representing the age group of 19 – 29. Most participants were male (88.1%). Conclusion: Blood group O and Rh+ factor was dominant in both sexes, Up-to-date knowledge of the distribution of blood types in a local setting is critical to the functioning of any national health service. To date, there has been a lack of data in Iraqi population.

Severe acute haemolytic transfusion reaction secondary to a plasma incompatible group B platelet transfusion.

To report a rare case of acute hemolytic transfusion reaction (AHTR) following an ABO plasma incompatible group B platelet transfusion. AHTR is an uncommon, but potentially fatal event. Most reported cases of platelet transfusions associated with AHTR involve group O donors. A 34-year-old man, recipient of a group AB haploidentical haematopoietic stem cell transplantation (HSCT), had received re-induction chemotherapy for leukaemia relapse. A group B whole blood-derived buffy coat platelet pool was transfused. He developed rigours/fever, profound hemolytic anaemia, and hemodynamic instability. Serological investigations revealed AHTR from passive transfer of high titre anti-A (256 for IgM and 8192 for IgG). This case highlights the potential risks associated with ABO-mismatched transfusions, and the complexity associated with transfusing HSCT recipients and red cell transfusion recipients with dual populations of circulating red cells. The literature on minor ABO plasma incompatible transfusions, challenges in establishing local policies to limit the risks of AHTR and risk mitigation strategies are discussed. Clinicians must maintain a high level of suspicion for AHTR after ABO plasma incompatible platelet transfusions. Patients must be aware of the risks of AHTR, and early recognition and diagnosis of this complication may be lifesaving.

Incidental Discovery of a Patient with the Bombay Phenotype.

Bombay phenotype, an exceptionally rare blood type in individuals outside of Southeast Asia, occurs in approximately 1 in 1,000,000 individuals in Europe. This blood phenotype is characterized by the absence of the H antigen on red blood cells (RBCs) and in secretions. As the H antigen is the structure on which the ABO system is built, individuals lacking this antigen are unable to produce A or B antigens and appear as type O on routine ABO phenotyping. H deficiency does not cause ill effect; however, these individuals produce an anti-H alloantibody capable of causing severe acute hemolytic transfusion reactions when exposed to RBCs that express the H antigen. In this case study, we highlight the incidental discovery of a patient with Bombay phenotype in a North American hospital system, expected test results, the immunologic and genetic basis underlying the Bombay and para-Bombay phenotypes, and methods to ensure availability of compatible blood.

Prevalence of Rhesus & Kell phenotypes among blood donors of Bangladesh

The Rhesus blood group system is one of the most polymorphic and highly immunogenic systems in humans. Because of its high and strong immunogenicity Rh D antigen testing is mandatory before issuing a compatible blood. There are five major antigens i.e. DCEce in the Rhesus (Rh) blood group system. On the other hand from the immunogenicity point of view Kell antigen is next to the Rh system. Both of them may cause severe hemolytic transfusion reaction and hemolytic disease of fetus and new born. Exposure of Rhesus negative individuals to Rhesus positive blood through transfusion or pregnancy is most likely to stimulate production of Rhesus antibodies. These antibodies may cause Hemolytic Disease of Fetus and Newborn (HDFN) and Delayed Hemolytic Transfusion Reaction (DHTR). Like Rhesus antibodies, Kell antibodies may also cause HDFN and DHTR. So far we know, there is not enough study regarding antigens C, c, E & e of Rh or K, k antigen of Kell blood group system regarding these antigens in the donors in Bangladesh, thereby exposing transfused patients to these antigens negative patients. To determine the phenotype prevalence of the Rh and Kell blood group systems in the blood donors in Bangladesh, a descriptive cross sectional study was done in the laboratory of Department of Transfusion Medicine, Bangabandhu Sheikh Mujib Medical University, during the period of 1st January 2020 to 31 December 2020. Rhesus Phenotype CCDee is highest (48.4%) & CCDEe & ccDEE both are lowest (0.4%). Most probable Rhesus Genotype CDe/CDe (R1R1) is highest (48.4%) and CDe/CDE (R1Rz) & cDE/cDE (R2R2) both are lowest (0.4%). Kell Genotype kk is highest (99.2%) and Kk is lowest (0.8%). BSMMU J 2021; 14(3): 38-42

Immunohematology and Transfusion Support of a Patient with Acute Myeloid Leukemia and an Anti-Vel

BackgroundTransfusion support of cancer patients presenting with red blood cell (RBC) antibodies against high-incidence antigens is a challenge for hospital-based Transfusion Services. For patients with antibodies against the high-frequency Vel antigen, only 0.0004% of blood donors will be Vel antigen-negative. Anti-Vel is notorious for looking like a benign, cold-reactive IgM antibody or a “high-titer, low-avidity” antibody; however, Vel-antibodies can fix complement at body temperatures and can cause severe hemolytic transfusion reactions. The immunohematology workup and RBC transfusion support are reported for a patient who developed an anti-Vel and other RBC antibodies during chronic transfusion therapy for myelodysplastic syndrome, with progression to acute myeloid leukemia. She was also evaluated for hematopoietic stem cell transplantation (HSCT).MethodsImmunohematologic workups were performed at a regional immunohematology reference laboratory. Since the patient had a positive autocontrol and a positive direct antiglobulin test (DAT), allogeneic adsorptions were performed at 37°C using R1R1, R2R2 and rr RBC reagents. Adsorbed plasma and eluates from adsorbed RBCs were then tested for alloantibody detection using manual tube method at both LISS and PEG reactivity. In preparation for possible HSCT, RBC alloantibody titers and monocyte monolayer assay (MMA) were performed. All samples were collected with pediatric phlebotomy tubes whenever possible.ResultsThe patient was a 66 year old woman with a myelodysplastic syndrome that transformed to acute myeloid leukemia (AML) with complex karyotype a year later. The RBC reference workup identified alloantibodies reacting to the high-incidence Vel antigen as well as low-incidence Yt(b) and Cw antigens. The patient's plasma was non-reactive with three of four Vel-negative (-) cells, whereas the reactive cell was Cw positive (+) and Yt(b+). Two allo-adsorptions were performed to remove anti-Vel. Upon repeat testing, anti-Cw was identified by LISS indirect antiglobulin test. Eluate from adsorbing RBCs was reactive with Vel- and Yt(b+) cells, suggesting presence of anti-Ytb. In preparation for HSCT, anti-Vel and anti-Cw were titered at 0 and 64, respectively. MMA for anti-Vel ranged at 0.2-2% (normal <3%). Nevertheless, the hospital-based Transfusion Service provided rare ABO/Rh Vel- CW- Yt(b-) crossmatch-compatible RBC to minimize the potential for stimulating anti-Vel, which might compromise a Vel+ HSCT. The patient required about 1 RBC unit per week to maintain hemoglobin above 4.5 g/dL. The Transfusion Service coordinated a search for antigen-negative RBCs with a national rare donor program, allowing at least 4 rare RBC units to be available at all times. Over an 18-month time period, the patient received 62 RBC Vel- units: 45 out of 62 (73%) were Cw- and 17 were Cw-unscreened but C-. Later in the patient's course, her transfusion rate increased to 2 RBC units per week. Because insufficient Vel- units were available within the USA, an international search by a rare donor program identified Vel- donors in Europe. FDA approval was obtained to import the rare units. She received 2 units from Spain and 2 units from Switzerland. Her leukemia progressed, and transfusion support was discontinued.ConclusionCoordination between hospital-based Transfusion Service, hematologists, and rare donor programs is required for rare RBC transfusion support in patients with antibodies against high-incidence antigens. A transfusion threshold of 4.5 g/dL may be tolerated when availability of rare RBC units is limited. DisclosuresNo relevant conflicts of interest to declare.

Use of a Hemoglobin Substitute (HBOC-201) to Treat Acute Anemia in a Leukemic Patient with Anti-Vel Antibodies

BackgroundThe Vel-negative blood type is a rare autosomal recessive trait, occurring in 1 in 4000 persons. It is extremely difficult to supply blood to patients with anti-Vel antibodies, and the situation is even more challenging for Vel-negative patients with leukemia who may have high transfusion needs. There are case reports of treatment with hemoglobin substitutes in Jehovah's Witnesses and surgical patients. To the best of our knowledge, we report the first use of a hemoglobin substitute, HBOC-1201 (HemoPure) to treat a patient with refractory acute myeloid leukemia (AML) and anti-Vel antibodies.Case ReportOur patient is a 67-year-old Caucasian man with a one-year history of acute myeloid leukemia, refractory to multiple hypomethylator- and chemotherapy-based regimens. History is also significant for coronary artery disease with type 2 NSTEMI due to severe anemia. He has experienced prolonged pancytopenia due to leukemia and chemotherapy and required blood transfusions approximately weekly. Anti-Vel antibodies make transfusion of compatible blood challenging, and we utilized a hemoglobin transfusion threshold of 5 g/dL. Working with the American Red Cross and the American Rare Donor Program (ARDP), we transfused 44 units of Vel-negative blood over a one-year period, depleting the available Vel-negative units in North America. He presented to the hospital with productive cough and dyspnea. Initial labs revealed acute on chronic anemia with hemoglobin 3.5 g/dL. CT of the chest revealed right lower lobe pneumonia. Given critical anemia in the setting of pneumonia and possible sepsis, the patient needed immediate blood transfusion. Compatible Vel-negative blood was not available in North America. While awaiting availability of international blood units through the Red Cross and ARDP, we considered the choices of 1) transfusing incompatible blood or 2) administering a blood substitute. Because individuals with anti-Vel antibodies may develop severe acute hemolytic transfusion reactions when transfused incompatible blood, we chose to treat with HBOC-1201 (Biopure Corporation, Cambridge, MA), a bovine hemoglobin polymer that lacks a red blood cell membrane and thus red cell antigens such as Vel. We obtained an emergency IND from the FDA and local IRB approval. Three 32-gram units of HBOC-1201 were successfully transfused, with hemoglobin rise from 3.5 to 4.5 g/dL. Common adverse effects associated with the use of acellular hemoglobin substitutes include increase in concentration of methemoglobin and vasopressor effects leading to elevated blood pressure, fluid overload, and myocardial infarction. Our patient was monitored closely and tolerated the transfusion without any apparent adverse events.ConclusionDuring a challenging clinical situation, we successfully treated severe acute anemia in a patient with refractory AML and anti-Vel antibodies, using the acellular bovine hemoglobin-based blood substitute HBOC-1201, when compatible blood was not available. The infusion was tolerated without complications. Hemoglobin substitutes may be considered as bridging treatments in critically anemic patients such as those with hematologic malignancies when red blood cell transfusion is not an option. DisclosuresNo relevant conflicts of interest to declare.

Prevalence of red blood cell antibodies in whole blood donors: A single-centre experience in north India.

Background & objectives:Blood transfusion therapy involves multiple steps to ensure selection of safe blood component for transfusion. This includes testing for infectious markers, full ABO compatibility, free from any clinically significant red cell antibodies and acceptable donor's red cell survival rates without destruction of recipient's red cells. The red cell antibodies present in healthy blood donors can cause severe haemolytic transfusion reaction, especially in massive blood transfusion recipients and paediatric patients. Hence, screening of red cell antibodies in donor blood is important to provide compatible blood products and to avoid haemolytic transfusion reactions in susceptible patient population. This study was planned to assess prevalence, aetiology and type of unexpected red cell antibodies in a large number of whole blood donor population in north India.Methods:This three-year prospective observational study included blood donor samples for antibody screening from January 2015 to December 2017. A total of 166,803 healthy blood donors including 156,128 (93.6%) males and 10,675 (6.4%) females were screened.Results:The prevalence of red cell antibodies was 0.17 per cent in our donor population. Of the total 286 donors with red cell antibodies, 248 (86.7%) had alloantibodies, 30 (10.5%) had autoantibodies and eight donors (2.8%) showed positive antibody screening with inconclusive results.Interpretation & conclusions:Alloimmunization to red cell antigens is a challenging task for current transfusion practices. The antibody screening in blood donors may improve the quality and safety of blood transfusion in the recipients. It also reduces the risk of complications from incompatible blood transfusions.

Prevalence of high titered anti-A and anti-B antibodies among O blood group individuals and their associated factors

Background and Objectives: Severe hemolytic transfusion reactions due to minor incompatibility are usually associated with the so-called “High titred” antibodies in the plasma of donors especially the O group as it is generally regarded as universal donors. Critical titers of 1:64 or higher was considered high titered antibodies for IgM anti-A and anti-B. Critical titers of 1:256 or higher was considered high titered antibodies for IgG anti-A and anti-B. The objective of this study was to see the prevalence of such high titered antibodies among our donor population and to observe for an association if any with the age, gender, and diet type and probiotic intake of the donors. Methodology: This was a cross-sectional analytical study conducted over 20 months from September 2015 to May 2017. About 560 donors were chosen randomly after screening and counseling and titration of anti-A and anti-B antibodies was done by the double dilution tube agglutination technique. The information on age, gender, diet type, and probiotic intake was gathered from the donor history questionnaire and an association between the factors described and the distribution of critical titers of anti-A and anti-B was elicited. Results: In the present study, the prevalence of high titer anti-A and anti-B IgM antibodies was 36% and 32%, respectively. The prevalence of high titer anti-A and anti-B IgG antibodies was 9.6% and 5.5%, respectively. The median IgM antibody titers reduced with the increasing age of the donors starting 18 years. There was a statistically significant association between a vegetarian diet and high titers. Conclusion: There are a considerable proportion of O group donors with high titers of antibodies and hence a routine pretransfusion screening for such antibodies can prevent the development of hemolytic reactions by segregating units into “high titer” and “low titer” antibodies and issuing only low titer products for out of group transfusions.

Blood Transfusion: a Guide to Clinical Decision Making

Nowadays, management of hemotherapy is regulated in Germany by the transfusion act and several guidelines while the transfusing physician is responsible for correct implementation at the bedside. Indications for blood products have to be carefully adapted to the patient's current clinical situation and pre-existing diseases have to be considered as well. Today, for most perioperative elective surgeries, evidence-based transfusion thresholds for packed red blood cell concentrates (RBC) have been defined and should be considered. Platelet concentrates (PC) have to be transfused in bleeding patients with thrombocytopenia or -pathy. In addition, PC are indicated prophylactically in clinically stable, not bleeding patients with a platelet trough count of less than 10/nl. Therapeutic plasma or fresh frozen plasma (FFP) is indicated for balanced substitution of coagulation factors, coagulation inhibitors and fibrinolysis factors in massive transfusion settings, where dilution of coagulation factors takes place. Plasma exchange in adults with thrombotic-thrombocytopenic purpura (TTP) or adult hemolytic-uremic syndrome (HUS) also requires FFP. In addition, FFP might be indicated, if no coagulation factor concentrate is available (e.g. FV deficiency). Adverse transfusion reactions are rare nowadays; however, hemolytic and allergic reactions are not too uncommon. For severe hemolytic transfusion reactions, in almost all cases, wrong blood in tube (WBIT) at the diagnostic bedside blood withdrawal or a mix-up of blood components before transfusion is causative. Massive transfusion situations require a proactive management, which includes RBC, FFP and potentially also PC and coagulation factor concentrates. Prior to elective surgery, anemic patients should be diagnosed and treated for the cause of their anemia, if possible.

Quality improvement with platelet additive solution for safer out-of-group platelet transfusions

Isoagglutinins in the plasma of apheresis platelets are a concern. High titer anti-A and anti-B can cause severe hemolytic transfusion reactions. Our facility is testing donor plasma using the gel method to identify isoagglutinin titers exceeding 250. Platelet additive solution (PAS), recently introduced as a collec-tion and storage solution, replaces approximately 65 percent of the plasma in a platelet component. We intended to confirm the effect of PAS on the isoagglutinin titers. We compared the isoagglutinin titers in donor plasma from EDTA-anticoagulated whole blood (without PAS) with the plasma in apheresis platelet components with PAS. Titers were determined in a buffered gel matrix test using serial twofold dilution steps. Among 100 donors tested, 26 plasma samples exceeded a threshold titer of 250; 25 were group O and only one was group B. When samples from these 26 platelet components with PAS were tested, only one group O donor exceeded the threshold titer. Samples from plasma components with PAS consistently showed a 50 percent decrease in titer compared with the donors' plasma samples. In conclusion, nearly half of the group O donors tested exceeded a titer of 250. Only one apheresis platelet component with PAS exceeded this clinically applied threshold-a 96 percent decrease compared with the number of donor plasma samples without PAS. The implementation of PAS in apheresis platelet components prompted us to revise our component screening process, which then minimized component manipulation of out-of-group platelet transfusions.

An update on the Scianna blood group system

This update of the Scianna blood group system (Brunker PA, Flegel WA. Scianna: the lucky 13th blood group system. Immunohematology 2011;27:41-57) provides the recent work on the genetic variation of ERMAP across more world populations, the elucidation of the molecular basis of an historical serologic case, new cases of antibodies in the system, the development of new serologic reagents, and new discoveries in the biology of the erythroid membrane associated protein (ERMAP). Although genetic variation in ERMAP has been extensively cataloged, nonsynonymous variants associated with alloantigens have remained limited, and no new antigens have been identified. The first case of a severe hemolytic transfusion reaction to anti-Sc2 has recently been reported, highlighting the importance of pursuing the possibility of antibodies to low-prevalence antigens via indirect antiglobulin testing as a routine component of all transfusion reaction investigations. The expanding use of molecular testing in blood centers and transfusion services has uncovered a wider population distribution of Scianna antigens and heightened the awareness of this blood group system. The International Society of Blood Transfusion recognizes seven antigens in the Scianna blood group system 13.

The First Comprehensive Study of H-Deficient Phenotypes in Iran

Background: The lack of correct blood grouping practices can lead to missing of the rare Bombay Oh phenotype and subjecting patients to the risk of severe hemolytic transfusion reaction. In the absence of blood donor registry, transfusion management of patients is a challenge. We performed this study in order to estimate the prevalence of the Bombay blood group (Oh) in Iran and to determine whether consanguinity plays a role in the prevalence of Oh group. Methods: This is a descriptive study in the Immunohematology Reference Laboratory of the Iranian Blood Transfusion Organization (IBTO) Tehran, Iran, over a period of 7 years. All donor blood samples showing blood group O and a strong initial reaction with blood group O RBC control cells were tested with anti-H lectin. Also blood samples from blood group O patients were tested with anti-H lectin if all cells on both antibody screening tests and antibody identification panels were reactive with negative auto control test. Specialized tests like adsorption/elution technique and inhibition assay for determination of secretor status were performed on Oh cases. Any history of consanguineous marriages were recorded. All variables were categorical variables, and percentage and proportions were calculated manually. Results: Analysis of the results of over 7 million first-time blood donors in Iran showed that the most common ABO blood group was O, with 2,520,000 (36%) subjects. 56 Oh individuals' (donors and patients) phenotypes (0.0008%) were detected. Consanguinity was observed in 50 cases (89%). Conclusions: This study shows that the prevalence of Bombay blood group in the general population of Iran is relatively high (0.0008%) and associated with consanguineous marriage. Thus, consanguinity is still an important risk factor present.

Complement Inhibition with C1 Esterase Inhibitor Allowed Successful Transfusion of Antigen Mismatched Packed Red Blood Cells : A Case Report

Hemolytic transfusion reactions (HTRs) occur after donor packed red blood cell (PRBCs) transfusions with antigenic differences including the major antigen system, ABO, as well as minor antigen systems such as Rh, Kell, Duffy, Kidd, JH, and U. These reactions are classified as acute if they occur within the first 24 hours or delayed if occurring after 24 hours. Antigen mismatched transfusions activate the classical pathway of complement leading to intravascular hemolysis via C5b-9 and extravascular hemolysis via C3b mediated phagocytosis in the spleen and liver (Stowell et al. Clin Devel Immunol 2012).In addition to laboratory evidence of hemolysis and increased antibody titers, patients can experience a wide range of clinical symptoms including fever, rash, chest, abdomen or back pain, signs of hemodynamic instability and death. (Strobel. Trans Med &amp; Hemo 2008) Mouse models have demonstrated that the inhibition of complement receptor 1 resulted in increased survival of mismatched transfused RBCs (Yazdanbakhsh et al. Blood 2003). The terminal complement inhibitor, eculizumab, has been used to successfully rescue a patient after a severe ABO incompatible hemolytic transfusion reaction (Weinstock et al. Transfusion 2015). Based on these data, we postulated that the prophylactic administration of a C1 esterase inhibitor would interrupt activation of the classical complement pathway, mitigating a hemolytic transfusion reaction to antigen mismatched PRBCs. A 50 year old African American male with widely metastatic prostate cancer presented with a hemoglobin (Hgb) of 5.1 g/dL and a platelet count of 39K/uL. His cytopenias had progressively worsened over the past 6 months from a baseline Hgb of 12 gm/dL and platelet count of 222 K/uL, and were secondary to bone metastases and prior spinal radiation. Thirty days prior to presentation, he received one unit of PRBCs at an outside institution for a Hgb of 7.0 g/dL. Due to worsening Hgb and clinical symptoms, a direct antiglobulin test (DAT) was obtained 21 days after the transfusion. It was noted to be positive for C3d suggesting a delayed hemolytic transfusion reaction. Upon type and cross match he was found to be O+ with new antibodies to Jka and U. A single compatible unit of PRBCs was identified and transfused. His Hgb increased from 4.5 g/dL to 5.9 g/dL with transfusion. His Hgb remained near 5g/dL over the next week however, he remained very symptomatic. There were no additional matched PRBCS available for transfusion despite a nationwide search. Given the dire clinical circumstances, it was decided to administer the commercially available C1-INH, Berinert®, prior to transfusion of antigen mismatched Jka-, U+ PRBCs. He received C1-INH 2500 units (roughly 20u/kg) prior to the first unit of Jka-, U+ PRBCs without clinical complication and improvement of Hgb from 5.4 g/dL to 7.1 g/dL. Twenty four hours later he received a second dose of C1-INH 2500 units followed by an additional unit of Jka-, U+ PRBCs. There were no clinical signs of a HTR, and the Hgb improved to 8.6g/dL. He received 5 additional doses of C1-INH in tapering doses in an attempt to prevent delayed HTR. The Hgb remained above 6 g/dL for the remainder of his hospital stay. The LDH initially increased from 642 units/L to 936 units/L 72 hours after the second premedicated mismatched transfusion. The haptoglobin level remained &lt; 8 mg/dL until 5 days post the second mismatched transfusion after which it returned to the normal range. The improvement in markers of hemolysis and stabilization of Hgb suggests that any further hemolysis related to the transfusion of the 2 Jka - U+ units was minimal and clinically insignificant. Quantification of anti U antibodies did not demonstrate an increase when evaluated 16 days post transfusion of U+ PRBCs. We present the first reported case where antigen mismatched PRBCs were safely transfused in conjunction with prophylactic complement inhibition with C1 esterase inhibitor. The transfusions were well tolerated, lacking clinical signs of hemolysis, and resulting in an appreciable and sustained improvement in Hgb. The additional observation of a stable anti U antibody titer 2 weeks after the transfusion of U+ PRBCs to U- patient is thought-provoking. Future directions would include clinical trials exploring complement inhibition's role in preventing HTRs and preventing alloantibody formation in heavily transfused patients. Table Table. Disclosures Broome: True North Therapeutics: Honoraria; Alexion Pharmaceuricals: Honoraria.

Immunological complications of blood transfusions

Most adverse blood transfusion (BT) events are immune-mediated and in the majority of severe reactions antibodies can be identified as causal factors. Alloimmunization not only causes symptomatic reactions, transfused cells can also be (silently) destroyed. Immunization by BT can contribute to hemolytic disease of the newborn as well as to allograft rejection after transplantation. Reversely, pregnancy and transplantation may evoke immunity hampering transfusion therapy. Besides causing mortality and morbidity, alloimmunization has a huge economic impact. Transfusion reactions prolong hospital stay, require diagnostic tests and complex donor selection procedures and create the need for typed donor registries. In the 1970s, Opeltz and colleagues described that pre-transplantation BT impaired rejection of renal transplants. Leukocytes were essential for this immunosuppressive BT effect that raised concern about negative effects on cancer growth and resistance against infections. Studies on the mechanism were however preliminary abandoned when calcineurin inhibitors for prevention of graft rejection became available and since all blood products underwent leukoreduction in most countries as precautionary measure against transmission of variant Creutzfeldt-Jacob disease. Whether current leukoreduced BT are immunosuppressive and for which patients or circumstances this may contribute to worse outcome, is unknown. The last decades of the previous century, leukoreduction of cellular blood products for leukemia patients significantly reduced the incidence of immunological platelet transfusion refractoriness. The first decade of this century the avoidance of plasma- and platelet-products from females, that may contain donor-derived leukocyte antibodies, decreased transfusion related acute lung injury (TRALI) by more than 30%. These were major achievements. Challenge for the near future is to further reduce alloimmunization in particular against red blood cells (RBC) as a cause of severe hemolytic transfusion reactions and problems to find compatible donors. This can be achieved by extended matching. Inventory limitations prevent to match all BT for clinically relevant RBC antigens. A (European-wide) registration of clinical and genetic risk factors associated with alloimmunization could support effective use of matched blood products.

The H blood group system

The H blood group system, ISBT symbol H (018), consists of a single antigen (H) defined by a terminal fucose residue found on red blood cells and in secretions formed by the action of α-1,2-fucosyltransferases 1 (α2FucT1) and 2 (α2FucT2), respectively. Mutant alleles of the corresponding FUT1 and FUT2 genes result in either a H– phenotype (Bombay phenotype, Oh) or a weak H phenotype (para-Bombay, H+w). In addition, the FUT2 gene is the molecular basis of the secretor (Se) status, and homozygosity or compound heterozygosity for null alleles is associated with the nonsecretor (se) status. H– individuals have natural anti-H (mostly IgM), which can cause severe hemolytic transfusion reactions with intravascular hemolysis.