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BACKGROUND Alloimmunization through blood transfusion, transplantation, or circulating fetal cells during pregnancy is a significant concern. Some exposed individuals make alloantibodies while others do not, implying variation in genetic risk factors. STUDY DESIGN AND METHODS We conducted a genomewide association study (GWAS) of 9,427,497 single-nucleotide polymorphisms (SNPs) to identify genetic variants for HLA alloimmunization in previously pregnant blood donors with (n = 752) and without (n = 753) HLA Class I or II alloantibodies. RESULTS A SNP in the neurexophilin 2 (NXPH2) gene surpassed genome-wide significance (p = 2.06 × 10-8 ), with multiple adjacent markers p

BACKGROUND Prevalence estimates of the serious hazards of transfusion vary widely. We hypothesized that the current reporting infrastructure in the United States fails to capture many transfusion reactions and undertook a multicenter study using active surveillance, data review, and adjudication to test this hypothesis. STUDY DESIGN AND METHODS A retrospective record review was completed for a random sample of 17% of all inpatient transfusion episodes over 6 months at four academic tertiary care hospitals, with an episode defined as all blood products released to a patient in 6 hours. Data were recorded by trained clinical research nurses, and serious reactions were adjudicated by a panel of transfusion medicine experts. RESULTS Of 4857 transfusion episodes investigated, 1.1% were associated with a serious reaction. Transfusion-associated circulatory overload was the most frequent serious reaction noted, being identified in 1% of transfusion episodes. Despite clinical notes describing a potential transfusion association in 59% of these cases, only 5.1% were reported to the transfusion service. Suspected transfusion-related acute lung injury/possible transfusion-related acute lung injury, anaphylactic, and hypotensive reactions were noted in 0.08, 0.02, and 0.02% of transfusion episodes, respectively. Minor reactions, including febrile nonhemolytic and allergic, were noted in 0.62 and 0.29% of transfusion episodes, respectively, with 30 and 50% reported to the transfusion service. CONCLUSION Underreporting of cardiopulmonary transfusion reactions is striking among academic, tertiary care hospitals. Complete and accurate reporting is essential to identify, define, establish pathogenesis, and mitigate/treat transfusion reactions. A better understanding of the failure to report may improve the accuracy of passive reporting systems.

Alloimmunization through blood transfusion, transplantation, or circulating fetal cells during pregnancy is a significant concern. Some exposed individuals make alloantibodies while others do not, implying variation in genetic risk factors.We conducted a genomewide association study (GWAS) of 9,427,497 single-nucleotide polymorphisms (SNPs) to identify genetic variants for HLA alloimmunization in previously pregnant blood donors with (n = 752) and without (n = 753) HLA Class I or II alloantibodies.A SNP in the neurexophilin 2 (NXPH2) gene surpassed genome-wide significance (p = 2.06 × 10Further work to extend the GWAS approach and to characterize variants in NXPH2 and E2F7 in the context of alloantibody formation is warranted.

Background and Objectives Human neutrophil antibodies (HNA) have been associated with severe transfusion-related acute lung injury (TRALI). We identified HNA antibodies in a blood donor population and performed an observational lookback on patients who received products from these donors to determine whether TRALI was associated with these transfusions. Materials and Methods Human neutrophil antibodies were determined in 1171 blood donors (388 non-transfused males, 390 human leucocyte antigen (HLA) antibody–negative females and 393 HLA antibody–positive females) for IgG and IgM antibodies using a flow cytometric assay. Selected positive samples had a monoclonal antibody immobilization of granulocyte antigen (MAIGA) and neutrophil genotyping performed to confirm specificity. Lookback was performed on patients receiving blood from donors with positive samples by extracting recipient data from hospital medical records. An expert panel of three pulmonary critical care physicians reviewed the summarized data and assigned a diagnosis of TRALI, possible TRALI, cannot distinguish between TRALI and TACO, TACO and other. Results Eight donors had HNA antibodies of which five contributed to this lookback (3-HNA-specific antibodies, 2-HNA non-specific antibodies). Seventy-six blood products were transfused from these donors into individual patients. One patient developed TRALI that was associated with a donor with a non-specific HNA antibody as well as class-I and class-II HLA antibodies. Conclusion The incidence of TRALI in this lookback was low and combined with low frequency of HNA antibodies in the donor population suggests not screening donors for HNA antibodies at this time is acceptable.

BACKGROUND: The importance of adverse reactions in terms of donor safety recently has received significant attention, but their role in subsequent donation behavior has not been thoroughly investigated. STUDY DESIGN AND METHODS: Six REDS-II blood centers provided data for this analysis. Summary minor and major adverse reaction categories were created. The influence of adverse reactions on donation was examined in two ways: Kaplan-Meier curves were generated to determine the cumulative pattern of first return, and adjusted odds ratios (AORs) for demographic and other factors positively and negatively associated with return were estimated using multivariable logistic regression. RESULTS: Donors who had major reactions had longer times to return than donors with minor or no reactions. The AOR of returning for donors with major reactions was 0.32 (95% confidence interval [CI], 0.28-0.37) and with minor reactions 0.59 (95% CI, 0.56-0.62) when compared to donors who did not have reactions. Conversely, the most important factors positively associated with return were the number of donations in the previous year and increasing age. Subsequent return, whether a major, minor, or no reaction occurred, varied by blood center. Factors that are associated with the risk of having adverse reactions were not substantial influences on the return after adverse reactions. CONCLUSION: Having an adverse reaction leads to significantly lower odds of subsequent donation irrespective of previous donation history. Factors that have been associated with a greater risk of adverse reactions were not important positive or negative predictors of return after a reaction.

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related deaths in the United States. Thirty-five percent of the deaths reported to the US Food and Drug Administration in the federal fiscal year 2008 were attributed to TRALI;1 this percentage decreased to 30% in the federal fiscal years 2009.2 The AABB issued an association bulletin on TRALI mitigation in November 2006 recommending that member blood centers minimize the preparation of high-plasma-volume components from donors known to be white blood cell (WBC) alloimmunized or at increased risk for WBC alloimmunization.3 In response to these recommendations, many blood collection agencies have restricted the distribution of plasma for transfusion to plasma that is derived from male donors as much as possible, with diversion of plasma from female donors to recovered plasma for use in manufacturing derivatives. While this approach is practical for blood group A and O plasma products, it might be more difficult to collect sufficient group B and AB plasma products exclusively from male donors to support the need for transfusable plasma. The AABB also recommended mitigation steps for apheresis platelet (PLT) components. However, there is no excess of apheresis PLT products from male donors; therefore, TRALI mitigation steps must consider alternative approaches for TRALI reduction than simply the use of male-only donors. In response to the need for data on the prevalence of WBC alloimmunization in blood donors, the National Institutes of Health–funded Retrovirus Epidemiology Donor Study-II (REDS-II) initiated an investigation of the prevalence of antibodies to human leukocyte antigens (HLA) and/or human neutrophil antigens (HNA) among blood donors from six geographically dispersed US blood collection centers. The REDS-II Leukocyte Antibody Prevalence Study-I (LAPS-I) reported that the prevalence of HLA Class I and/or HLA Class II antibodies was similar in nontransfused (1.0%) versus transfused men (1.7%) and that 24.4% of female donors with a history of a previous pregnancy had HLA antibodies.4 This study estimates the prevalence of WBC alloimmunization according to the pregnancy and transfusion history of allogeneic blood donors at each of the REDS-II blood centers. These data, together with the data from the LAPS-I study,4 were used to compare the impact of the implementation of the AABB TRALI mitigation strategies among six different blood centers.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. Blood centers are implementing TRALI risk reduction strategies based on screening apheresis donors for antibodies to human leukocyte antigens (HLA). STUDY DESIGN AND METHODS: HLA antibody screening was performed on 7920 blood donors from the Leukocyte Antibody Prevalence Study (LAPS) using Luminex-based normalized background (NBG) cutoff ratios of 10.8 (Class I) and 6.9 (Class II). Single antigen bead (SAB) assay cutoffs of 2500 median fluorescence intensity units (Class I) and 1500 (Class II) were established based on results of two subpopulations of LAPS donors. Antibody frequencies against HLA A, B, C, DR, DQ, and DP antigens were determined for screen-reactive donors with prior pregnancies. RESULTS: SAB reactivity for samples above our multiantigen bead NBG cutoffs was 78% for Class I and 79% for Class II. The SAB-positive rate increased among women with zero to four or more pregnancies (0.3%-15.6% Class I and 0.4%-18% Class II; p

BACKGROUND: HLA antibody testing of previously transfused or pregnant donors may help reduce the risk of transfusion-related acute lung injury (TRALI). However, the prevalence of HLA antibodies in transfused donors has not been well characterized. STUDY DESIGN AND METHODS: Transfusion and pregnancy history was obtained from consenting donors. HLA Class I and II antibody testing was performed by multiantigen bead Luminex platform. Cutoff values for Class I and II antibodies used normalized background ratios of 10.8 and 6.9, respectively. Linear probability models were used to evaluate potential associations between HLA alloimmunization and donor characteristics. RESULTS: A total of 7920 donors (2086 males and 5834 females) were tested. HLA antibody prevalence did not significantly differ between 895 transfused (1.7%) and 1138 nontransfused males (1.0%; odds ratio [OR], 1.75; 95% confidence interval [CI], 0.80-3.82]. Prevalence in 45 transfused nulliparous females (4.4%; 95% CI, 0.1%-11.8%) was not different from the 1.6% prevalence in 1732 nontransfused nulliparous females (OR, 2.94; 95% CI, 0.68-12.74). Transfused parous females had higher prevalence than nontransfused counterparts (p = 0.004; OR, 1.39; 95% CI, 1.07-1.80). In a linear probability model, the estimated additive risk of transfusion-induced alloimmunization was only 0.8% (95% CI, −0.2% to 1.8%; p = 0.10). Donor transfusion history showed that 58% of transfusions occurred more than 10 years previously. CONCLUSION: Transfused volunteer blood donors do not appear to have a significantly higher prevalence of HLA antibodies than their nontransfused counterparts. Thus, in an effort to reduce TRALI risk, ascertaining past history of transfusion and testing these donors for HLA antibodies is not necessary.

BACKGROUND: Antibodies to human leukocyte antigens (HLA) in donated blood have been implicated as a cause of transfusion-related acute lung injury (TRALI). A potential measure to reduce the risk of TRALI includes screening plateletpheresis donors for HLA antibodies. The prevalence of HLA antibodies and their relationship to previous transfusion or pregnancy in blood donors was determined. STUDY DESIGN AND METHODS: A total of 8171 volunteer blood donors were prospectively recruited by six US blood centers from December 2006 to May 2007. Donors provided a detailed history of pregnancy and transfusion and a sample for HLA Class I and II antibody testing by multiantigen bead flow analysis. RESULTS: A total of 8171 donors were enrolled; 7920 (96.9%) had valid HLA antibody test results and 7841 (99%) of those had complete pregnancy and transfusion information. The prevalence of any HLA antibody was similar in nontransfused (n = 1138) and transfused (n = 895) men, 1.0% versus 1.7% (p = 0.16). HLA antibodies were detected in 17.3% of all female donors (n = 5834) and in 24.4% of those with a history of previous pregnancy (n = 3992). The prevalence of HLA antibodies increased in women with greater numbers of pregnancy: 1.7% (zero), 11.2% (one), 22.5% (two), 27.5% (three), and 32.2% (four or more pregnancies; p < 0.0001). CONCLUSION: HLA Class I and Class II antibodies are detectable at low prevalence in male donors regardless of transfusion and in female donors without known immunizing events. The prevalence of HLA antibodies increases significantly with more pregnancies. These data will allow blood centers to estimate the impact of HLA antibody testing as a potential TRALI risk reduction measure.

BACKGROUND: Primary care physicians commonly care for patients whose disabilities caused by cardiovascular diseases result in difficulty driving an automobile. Patients often seek their physician's advice as to whether they can continue to drive safely. METHODS: A MEDLINE literature search was performed from 1966 to 2000, using the query terms "automobile driving" and "automobile driving and cardiac." Selected articles were reviewed, as well as additional articles found through review of the references. In some cases articles were found by searching the Internet using the above key words and new query terms guided by the results of the original search. RESULTS AND CONCLUSIONS: The most important factor determining eligibility is whether the patient reports manifestations of cerebral hypoxia. Laboratory procedures are available for patients in whom the decision is difficult. Sometimes a referral to a specialist is needed. Many patients with a known cardiovascular disorder can continue to drive safely. Some conditions require a waiting period before driving can be resumed, while others call for a complete cessation of driving. Several guidelines from the literature are listed that can be helpful to primary care physicians when dealing with questions from their patients on this important topic. Language: en

A 24-year old female, gravida ΠI, para ΠI, delivered a full-term infant by cesarean section. A maternal blood sample at the time of admission showed antibody in her serum that had apparent anti-e specificity and that her RBCs were e+. Further studies determined that the antibody was anti-hrs. Cord RBCs had a negative DAT and a normal Hb level. There was no clinical evidence for increased hemolysis in the infant. We describe an hrs+ infant with no evidence of HDN due to anti-hr5.

Anti-Ku seen in K0(Kell-null) individuals has previously been shown to cause severe hemolytic transfusion reactions. Maternal anti-Ku can cause none or moderate to severe hemolytic disease of the fetus and newborn (HDFN). In two of four previously described HDFN cases, intrauterine transfusions were required because of severe anemia. We report a case in which maternal anti-Ku did not cause HDFN. Standard serologic methods were used for RBC antibody screening and identification, adsorption and elution of RBC antibodies, and antigen typing. A gravida 3, para 3 (G3P3) woman was first evaluated in 2006 and was found to have an IgG RBC antibody that reacted against all panel RBCs in the anti-human globulin phase. A panel of RBCs treated with DTT did not react with the antibody. The antibody failed to react with one example of K0 RBCs. The patient’s RBCs typed negative for the following Kell blood group antigens: KEL1, KEL2, KEL3, KEL4, KEL6, KEL7, KEL11, KEL13, and KEL18. These results established the presence of anti-Ku in maternal serum. The newborn was group A, D+ and required phototherapy for hyperbilirubinemia, but did not require transfusion. The woman was seen again in January 2010 during the third trimester (G4P3). At this time, anti-Ku titer was 256. She delivered a healthy group O, D+ baby boy at 37 weeks’ gestation. Cord RBCs were 4+ for IgG by DAT. An eluate reacted with all RBCs tested, but did not react when tested against a panel of DTT-treated RBCs. K0phenotype is rare to begin with, and the maternal anti-Ku formation may require more than one pregnancy. Therefore, cases that can be evaluated for anti-Ku–related HDFN are rare. Our case contributes to serologic and clinical aspects of such rare cases. Immunohematology 2010;26:119–122.

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. Blood centers are implementing TRALI risk reduction strategies based on screening apheresis donors for antibodies to human leukocyte antigens (HLA).HLA antibody screening was performed on 7920 blood donors from the Leukocyte Antibody Prevalence Study (LAPS) using Luminex-based normalized background (NBG) cutoff ratios of 10.8 (Class I) and 6.9 (Class II). Single antigen bead (SAB) assay cutoffs of 2500 median fluorescence intensity units (Class I) and 1500 (Class II) were established based on results of two subpopulations of LAPS donors. Antibody frequencies against HLA A, B, C, DR, DQ, and DP antigens were determined for screen-reactive donors with prior pregnancies.SAB reactivity for samples above our multiantigen bead NBG cutoffs was 78% for Class I and 79% for Class II. The SAB-positive rate increased among women with zero to four or more pregnancies (0.3%-15.6% Class I and 0.4%-18% Class II; p0.00001). The highest frequency antibodies were DR11 and B15 (4.4% of women with prior pregnancies). The majority of Class I positives contained more than five specificities. For Class II, antibody-positive women segregated into two groups: a single specificity or more than five specificities.Identification of HLA antigen specificities supports pregnancy associations previously found with screening assays. The significance of particular HLA specificities for inducing TRALI is currently being evaluated in a large lookback study of recipients of high-plasma-volume components from this donor cohort.

An immune complex mechanism for ceftriaxone sodium– induced severe autoimmune hemolytic anemia has previously been demonstrated using routine blood bank techniques. We describe herein a patient with severe hemolysis that subsided once the drug was discontinued. Serologic techniques demonstrated immune complex–mediated ceftriaxone-dependent red cell antibodies. These findings were further supported by the results of flow cytometry, in which a change in basal red cell autofluorescence was seen in the presence of the antibody and the drug. Our case illustrates the adjunctive value of flow cytometry in the diagnosis of ceftriaxone-dependent red cell antibody.

A survey of 19 large blood centers, each with an average annual collection of 158,889 units, was conducted to identify current practices of management of red cell units that contain unexpected red cell antibodies. The routine antibody identification, distribution, and charge for such units varied widely among the 19 centers. In addition, although use of these units was low, costs were considerable. This survey can serve as a basis for other studies to arrive at cost-effective ways to manage such units. Immunohematology 1994;10:99–101.

Background: Our blood center began routine screening of Single Donor Platelets, Pheresis (SDP) for bacteria on December 15, 2003 using aerobic culture bottles with the BacT Alert® 3D System. SDP units are held a minimum of 24 hours prior to sampling and then are labeled and released while the culture bottles are incubated for five days. Case Study: A 77-year old female donated a SDP and concurrent Plasma. Pre-donation platelet count was 328 x103/μL and hemoglobin level was 15.0 g/dL. Collection was uneventful with no error codes received from the equipment. Sample for was obtained on day-1, inoculated in an aerobic culture bottle, and incubated. The inoculated bottle showed growth of bacteria at 19.6 hours of the culture period. SDP had not been distributed and was recultured. Repeat culture was performed on day-2 and it also showed growth at 13.4 hours. The concurrent plasma was thawed and cultured and did not show any growth. A gram stain of the positive culture bottle revealed gram-positive cocci in chains that were later identified as Streptococcus viridans. The donor was notified of the culture results. The donor denied any skin rash or infection, sore throat, fractures, heart or lung conditions. She denied fever, chills or any acute illness. Her chronic conditions included hypertension treated with Lisinopril. She was also receiving thyroid replacement for hypothyroidism and Asiphex for gastro esophageal reflux disease (GERD). She denied any GI or GU symptoms. The culture results were mailed to the donor so that she could share them with her personal physician. The donor is a frequent apheresis donor and has donated 54 SDPs over the past seven years. Three previous donations immediately prior to the current donation were found to be negative after 5-day culture. On day 18, the donor felt weak and tired but without fever or other symptoms and she went to see her physician. The physician obtained a blood culture that grew bacteria the next day. Further testing identified the organism as Streptococcus salivarius, a viridans species. Donor was then hospitalized for five days to begin intravenous Ceftriaxone. Further antibiotic treatment was given at home via a peripherally inserted central (PIC) line. The donor had a three-year history of a benign heart murmur. The PIC line was removed with the completion of the antibiotic treatment on day 65. The donor remained asymptomatic throughout the treatment. Two trans-thoracic and two trans-esophageal echocardiograms were negative for bacterial endocarditis. However, mild idiopathic hypertrophic subaortic stenosis was discovered. The donor had dental work done two months prior to the time the bacteremia was found. However, she had one SDP donation that was culture negative after the dental work. The cause of the donor’s bacteremia remains obscure. Discussion: Although the screening of Platelets, Pheresis is for the protection of the patient who will receive the product, this case shows that the detection of the bacteria also may benefit the donor. In our case, aymptomatic Streptococcus viridans bacteremia would not have been recognized if it were not detected by culturing her SDP. The donor was grateful for the information that lead to the early detection of blood stream infection that resulted in successful treatment. The donor continues to ask that she be able to donate when eligible.

Reactivity of high-incidence antigens after glycine-EDTA treatment of red blood cells (RBCs) to prepare artificial Ko RBCs was investigated. The treatment had little or no effect on Yta, JMH, Yka, Kna, and McCa. Hy antigen-positive-treated RBCs reacted less well with anti-Hy when compared to nontreated cells. Glycine-EDTA treatment to prepare Ko RBCs offers an advantage over AET treatment because it preserves some high-frequency antigens that AET treatment does not.

A pheresis procedure was devised to isolate young red cells by centrifugation using the Fenwal CS 3000 continuous flow cell separator. Young red cell enriched products were collected in a 2.5-3-hour procedure. Large numbers of white cells and platelets were collected with the red cells, but cryopreservation and subsequent washing removed 99% of the contaminating cells. At the completion of all processing a product yielding 70% of the total hemoglobin content of a standard frozen/deglycerolized red cell unit was produced. Autologous radiochromium survival of young red cells, measured in 12 normal donors, showed an average 24-hour recovery of 89.9% with a T50Cr of 40.8 days. In paired autologous studies (N = 4) there was a mean increase of 35% in the observed T50Cr of young red cells as compared to standard frozen red cells.