Objectives

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) disproportionately affect women during and following childbearing years. Antihuman leucocyte antigen (HLA) alloantibody responses are common in healthy parous women, and as these diseases are both linked with HLA and immune dysregulation, we sought to evaluate anti-HLA antibodies in RA and SLE.

Methods

Anti-HLA antibodies were measured among parous SLE cases (n=224), parous RA cases (n=202) and healthy parous controls (n=239) and compared with each other as well as with nulliparous female and male controls. Antibody specificities were identified and compared against subject HLA types to determine autoreactivity versus alloreactivity. The association of anti-HLA antibodies with clinical outcomes was evaluated.

Results

Levels and frequencies of anti-HLA antibodies were significantly higher among parous females with SLE (52%) or RA (46%) compared with controls (26%), and anti-HLA antibodies were also found among nulliparous females and males with SLE and RA. Autoreactive anti-HLA antibodies were observed among SLE and RA antibody-positive subjects, but not healthy controls, with the highest frequency of autoreactive anti-HLA antibodies found in the SLE subjects. Higher levels of anti-HLA antibodies were associated with nephritis among the nulliparous SLE cases (p<0.01). The presence of anti-class I HLA antibodies was associated with younger age at diagnosis among both the RA and SLE nulliparous cases.

Conclusions

Both autoreactive and alloreactive anti-HLA antibodies were found at high levels in RA and SLE subjects. These occurred even in the absence of alloexposure, particularly among SLE subjects and may be linked with disease severity.

Background:Randomized clinical trial findings support decreased red blood cell (RBC) transfusion and short-term tolerance of in-hospital anemia. However, long-term outcomes related to changes in transfusion practice have not been described. Objective:To describe the prevalence of anemia at and after hospital discharge and associated morbidity and mortality events. Design:Retrospective cohort study. Setting:Integrated health care delivery system with 21 hospitals serving 4 million members. Participants:445 371 surviving adults who had 801 261 hospitalizations between January 2010 and December 2014. Measurements:Hemoglobin levels and RBC transfusion, rehospitalization, and mortality events within 6 months of hospital discharge. Generalized estimating equations were used to examine trends over time, accounting for correlated observations and patient-level covariates. Results:From 2010 to 2014, the prevalence of moderate anemia (hemoglobin levels between 7 and 10 g/dL) at hospital discharge increased from 20% to 25% (P < 0.001) and RBC transfusion declined by 28% (39.8 to 28.5 RBC units per 1000 patients; P < 0.001). The proportion of patients whose moderate anemia had resolved within 6 months of hospital discharge decreased from 42% to 34% (P < 0.001), and RBC transfusion and rehospitalization within 6 months of hospital discharge decreased from 19% to 17% and 37% to 33%, respectively (P < 0.001 for both). During this period, the adjusted 6-month mortality rate decreased from 16.1% to 15.6% (P = 0.004) in patients with moderate anemia, in parallel with that of all others. Limitation:Possible unmeasured confounding. Conclusion:Anemia after hospitalization increased in parallel with decreased RBC transfusion. This increase was not accompanied by a rise in subsequent RBC use, rehospitalization, or mortality within 6 months of hospital discharge. Longitudinal analyses support the safety of practice recommendations to limit RBC transfusion and tolerate anemia during and after hospitalization. Primary Funding Source:National Heart, Lung, and Blood Institute.

The United States Food and Drug Administration Final Guidance for Industry titled, "Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion" provides nine strategies for platelet bacterial risk mitigation. Even if it is assumed all strategies are comparable in terms of safety and efficacy, the decision of which to implement remains challenging. Some additional factors that warrant evaluation before selecting a strategy include the financial impact, process for implementation, logistics upon implementation, institutional acceptance by blood bank staff, administration and clinicians, and effect on platelet availability. To assist with this difficult choice, a panel of transfusion service physicians who have expertise on the topic and have already selected strategies for their transfusion services were recruited to provide varied perspectives. In addition, the use of a decision-making tool that objectively evaluates defined criteria for assessment of the nine strategies is described.

OBJECTIVES:Transfusion-associated circulatory overload is characterized by hydrostatic pulmonary edema following blood transfusion. Restrictive transfusion practice may affect the occurrence and severity of transfusion-associated circulatory overload in critically ill patients. We sought to examine contemporary risk factors and outcomes for transfusion-associated circulatory overload. DESIGN:Case-control study. SETTING:Four tertiary care hospitals. PATIENTS:We prospectively enrolled 200 patients with transfusion-associated circulatory overload identified by active surveillance and 405 controls matched by transfusion intensity. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Among 20,845 transfused patients who received 128,263 blood components from May 2015 until July 2016, transfusion-associated circulatory overload incidence was one case per 100 transfused patients. In addition to cardiovascular comorbidities, multivariable analysis identified the following independent predictors of transfusion-associated circulatory overload: acute kidney injury, emergency surgery, pretransfusion diuretic use, and plasma transfusion-the latter especially in females. Compared with matched controls, transfusion-associated circulatory overload cases were more likely to require mechanical ventilation (71% vs 49%; p < 0.001), experienced longer intensive care and hospital lengths of stay following transfusion, and had higher mortality (21% vs 11%; p = 0.02) even after adjustment for other potentially confounding variables. CONCLUSIONS:Despite restrictive transfusion practice, transfusion-associated circulatory overload remains a frequent complication of transfusion and is an independent risk factor for in-hospital morbidity and mortality. In addition to cardiovascular and renal risk factors, plasma transfusion was associated with transfusion-associated circulatory overload after controlling for other covariates. Additional research is needed to examine the benefit of reduced erythrocyte or plasma exposure in patients at high risk for transfusion-associated circulatory overload.

Despite the significance of red blood cell (RBC) alloimmunization, the lack of standardized registries in the US has prevented the completion of large studies. Data from 3·5 years of the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) recipient database, containing information from 12 hospitals, were studied. A RBC alloantibody responder had an antibody identified at any point during the study, and a non-responder had a negative antibody screen at least 15 days post-RBC transfusion. Demographics, blood type, ICD9/10 codes, and other potential correlates were evaluated. Of 319 177 (2·07%) screened patients, 6597 had a total of 8892 clinically significant RBC alloantibodies identified, with 75% being in the Rh or Kell families. Alloimmunization was more common in females (2·38%) than males (1·68%), and in RhD negative (2·82%) than RhD positive (1·94%) patients. Age, sex, RhD status and race were associated with being a responder, and certain diagnoses (including sickle cell disease or trait, systemic lupus erythematosus, rheumatoid arthritis and myelodysplastic syndrome) were more common among responders than non-responders. Data collected in this multi-centre recipient database provide the largest RBC alloimmunized patient cohort studied in the US, with previously known demographic and disease associations of responder status confirmed, and new associations identified.

Significant research has focused individually on blood donors, product preparation and storage, and optimal transfusion practice. To better understand the interplay between these factors on measures of red blood cell (RBC) transfusion efficacy, we conducted a linked analysis of blood donor and component data with patients who received single-unit RBC transfusions between 2008 and 2016. Hemoglobin levels before and after RBC transfusions and at 24- and 48-hour intervals after transfusion were analyzed. Generalized estimating equation linear regression models were fit to examine hemoglobin increments after RBC transfusion adjusting for donor and recipient demographic characteristics, collection method, additive solution, gamma irradiation, and storage duration. We linked data on 23 194 transfusion recipients who received one or more single-unit RBC transfusions (n = 38 019 units) to donor demographic and component characteristics. Donor and recipient sex, Rh-D status, collection method, gamma irradiation, recipient age and body mass index, and pretransfusion hemoglobin levels were significant predictors of hemoglobin increments in univariate and multivariable analyses (P < .01). For hemoglobin increments 24 hours after transfusion, the coefficient of determination for the generalized estimating equation models was 0.25, with an estimated correlation between actual and predicted values of 0.5. Collectively, blood donor demographic characteristics, collection and processing methods, and recipient characteristics accounted for significant variation in hemoglobin increments related to RBC transfusion. Multivariable modeling allows the prediction of changes in hemoglobin using donor-, component-, and patient-level characteristics. Accounting for these factors will be critical for future analyses of donor and component factors, including genetic polymorphisms, on posttransfusion increments and other patient outcomes.

Systemic lupus erythematosus (SLE) disproportionately affects women of reproductive age. During pregnancy, women are exposed to various sources of fetal material possibly constituting a significant immunologic exposure relevant to the development of SLE. The objective of this study was to investigate whether having any children who carry DRB1 alleles associated with SLE increase the risk of maternal SLE. This case-control study is based on the University of California, San Francisco Mother-Child Immunogenetic Study and from studies at the Inova Translational Medicine Institute. Analyses were conducted using data for 1304 mothers (219 cases/1085 controls) and their respective 1664 children. We selected alleles based on their known association with risk of SLE (DRB1*03:01, *15:01, or *08:01) or Epstein-Barr virus (EBV) glycoproteins (*04:01) due to the established EBV association with SLE risk. We used logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for each allele of interest, taking into account maternal genotype and number of live births. We found an increase in risk of maternal SLE associated with exposure to children who inherited DRB1*04:01 from their father (OR 1.9; 95% CI, 1.1-3.2), among *04:01 allele-negative mothers. Increased risk was only present among mothers who were positive for one or more SLE risk-associated alleles (*03:01, *15:01 and/or *08:01). We did not find increased risk of maternal SLE associated with any other tested allele. These findings support the hypothesis that a child's alleles inherited from the father influence a mother's subsequent risk of SLE.

Background

Blood conservation strategies have been shown to be effective in decreasing red blood cell (RBC) utilization in specific patient groups. However, few data exist describing the extent of RBC transfusion reduction or their impact on transfusion practice and mortality in a diverse inpatient population.

Study design and methods

We conducted a retrospective cohort study using comprehensive electronic medical record data from 21 medical facilities in Kaiser Permanente Northern California. We examined unadjusted and risk-adjusted RBC transfusion and 30-day mortality coincident with implementation of RBC conservation strategies.

Results

The inpatient study cohort included 391,958 patients who experienced 685,753 hospitalizations. From 2009 to 2013, the incidence of RBC transfusion decreased from 14.0% to 10.8% of hospitalizations; this change coincided with a decline in pretransfusion hemoglobin (Hb) levels from 8.1 to 7.6 g/dL. Decreased RBC utilization affected broad groups of admission diagnoses and was most pronounced in patients with a nadir Hb level between 8 and 9 g/dL (n = 73,057; 50.8% to 19.3%). During the study period, the standard deviation of risk-adjusted RBC transfusion incidence across hospitals decreased by 44% (p < 0.001). Thirty-day mortality did not change significantly with declines in RBC utilization in patient groups previously studied in clinical trials nor in other subgroups.

Conclusions

After the implementation of blood conservation strategies, RBC transfusion incidence and pretransfusion Hb levels decreased broadly across medical and surgical patients. Variation in RBC transfusion incidence across hospitals decreased from 2010 to 2013. Consistent with clinical trial data, more restrictive transfusion practice did not appear to impact 30-day mortality.

Background

Recent publications have reported conflicting findings regarding associations of blood donor demographics and mortality of transfused patients. We hypothesized that the analysis of additional donor characteristics and consideration of alternative outcomes might provide insight into these disparate results.

Study design and methods

We analyzed data from a retrospective cohort of transfused patients from the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). We used stratified Cox regression models to estimate associations between blood donor characteristics and hospital mortality and posttransfusion length of stay among patients transfused red blood cell (RBC) units. Donor characteristics evaluated included age, body mass index, hemoglobin levels, and smoking status. The statistical analyses were adjusted for recipient factors, including total number of transfusions.

Results

We studied 93,726 patients in 130,381 hospitalizations during which 428,461 RBC units were transfused. There were no associations between blood donor characteristics and hospital mortality. Receipt of RBC units from donors less than 20 years of age was associated with a shorter hospital length of stay (hazard ratio for discharge per transfused unit, 1.03; 95% confidence interval, 1.02-1.04; p < 0.001) but not for other donor characteristics.

Conclusion

We found no evidence of associations between blood donor factors and in-hospital mortality. Our finding of shorter hospital length of stay in patients transfused RBCs from younger donors is intriguing but requires confirmation. Future collaborations are needed to develop a framework of appropriate methodologic approaches to be used in linked analyses across large cohorts.

Background

Transfusion-related acute lung injury (TRALI) mitigation strategies include the deferral of female donors from apheresis platelet (PLT) donations and the distribution of plasma for transfusion from male donors only. We studied the implications of these policies in terms of component loss at six blood centers in the United States.

Study design and methods

We collected data from allogeneic blood donors making whole blood and blood component donations during calendar years 2006 through 2008. We analyzed the distribution of donations in terms of the sex, transfusion and pregnancy histories, and blood type.

Results

A TRALI mitigation policy that would not allow plasma from female whole blood donors to be prepared into transfusable plasma components would result in nearly a 50% reduction in the units of whole blood available for plasma manufacturing and would decrease the number of type AB plasma units that could be made from whole blood donations by the same amount. Deferral of all female apheresis PLT donors, all female apheresis PLT donors with histories of prior pregnancies, or all female apheresis PLT donors with histories of prior pregnancies and positive screening test results for antibodies to human leukocyte antigens (HLAs) will result in a loss of 37.1, 22.5, and 5.4% of all apheresis PLT donations, respectively.

Conclusion

A TRALI mitigation policy that only defers female apheresis PLT donors with previous pregnancies and HLAs would result in an approximately 5% decrease in the inventory of apheresis PLTs, but would eliminate a large proportion of components that are associated with TRALI.