Early and sustained improvement in fatigue-related quality of life following red blood cell transfusion in outpatients.

PURPOSE: Outpatients with hematologic disease often receive red cell transfusion to treat anemia and fatigue. The effect of transfusion on fatigue-related quality of life and how well this effect is sustained has not been quantified. The study aim was to describe the early and sustained impact over 4 weeks of red cells on patient-reported fatigue in outpatients age ≥ 50 receiving transfusion as routine clinical care. METHODS: FACIT-Fatigue scale scores were measured pre-transfusion and at visits targeting 3, 7, and 28 days post-transfusion. Group-based trajectory modeling of patient fatigue scores by study day was used to identify the number of distinct trajectories (Groups), then longitudinal mixed effects modeling of fatigue scores was used to estimate group-specific mean improvements early after transfusion and between days 3 and 28 post-transfusion. RESULTS: Four distinct fatigue score trajectory groups were identified and were found to be correlated with baseline fatigue scores (means 12, 26, 34, and 47 points). In the three groups with the lowest fatigue trajectories (indicating greater fatigue), improvements in fatigue early after transfusion achieved the established minimum clinically important difference (≥ 3 points, Group p = 0.0039). In all trajectory groups, mean fatigue levels did not change significantly between 3 and 28 days (± 1 point, Group p = 0.60). CONCLUSION: Patient-reported fatigue varies widely among older adult outpatients with hematologic disorders. Nonetheless, trajectory modeling suggests that most anemic patients can expect a noticeable improvement in fatigue in the first few days after transfusion that generally is sustained up to 4 weeks.

Association of donor age, body mass index, hemoglobin, and smoking status with in-hospital mortality and length of stay among red blood cell-transfused recipients.

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.

The impact of recipient factors on the lower-than-expected hemoglobin increment in transfused outpatients with hematologic diseases.

BACKGROUND: Patients with cancer or chronic hematologic disorders frequently receive red blood cell (RBC) transfusions. Based on long-standing assumptions, each RBC unit is thought to increase recipient hemoglobin by 1 g/dL, but smaller increments can occur. A better understanding of recipient factors affecting hemoglobin increments could help providers manage these patients. METHODS: Data were collected as a part of the observational Red Cells in Outpatients Transfusion Outcomes (RETRO) study of outpatients with hematologic or cancer-related diagnoses. Hemoglobin was measured before transfusion and 30 minutes after transfusion. A classification and regression tree (CART) analysis was performed to identify statistically significant associations with clinical variables. A corresponding prediction equation was developed and validated using linear regression. RESULTS: A total of 195 participants had both pre- and posttransfusion hemoglobin values for analysis. The median age was 66 years, and patients received one (73%) or two (27%) RBC units during the transfusion episode. The overall median change in hemoglobin was 0.6 g/dL per RBC unit. Both CART analysis and linear regression identified the following significant predictors of hemoglobin increment: number of units received (positive correlation), patient estimated circulating blood volume (negative correlation), pretransfusion hemoglobin (negative correlation), and patient age (negative correlation). CONCLUSION: In this study of outpatients with hematologic disease, most patients had a hemoglobin increment of less than 1 g/dL/unit. Recipient-specific factors influenced the hemoglobin increment at 30 minutes, and providers should consider circulating blood volume, pretransfusion hemoglobin, and recipient age, when developing patient-specific RBC transfusion plans for this unique cohort.

Association of Blood Donor Sex and Prior Pregnancy With Mortality Among Red Blood Cell Transfusion Recipients.

Importance: Evidence regarding associations of blood donor sex with mortality among red blood cell transfusion recipients is conflicting. Objective: To study associations of donor sex and prior pregnancy with mortality of transfusion recipients. Design, Setting, and Participants: Data from 3 retrospective cohorts of transfusion recipients (the Kaiser Permanente Northern California [KPNC] and Recipient Epidemiology and Donor Evaluation Study-III [REDS-III] databases of data from January 2013 to December 2016 and the Scandinavian Donations and Transfusions [SCANDAT] database with data from January 2003 to December 2012) were analyzed. Final dates of follow-up were December 31, 2016, for the KPNC and REDS-III cohorts and December 31, 2012, for the SCANDAT cohort. Stratified Cox regression models were used to estimate associations between donor exposure groups with risk of mortality, adjusting for the number of red blood cell unit transfusions. Exposures: The number of transfused red blood cell units from female donors, previously pregnant donors, and sex-discordant donors (male donor and female recipient or female donor and male recipient). Main Outcomes and Measures: In-hospital mortality. Results: The study population included 34 662 patients (mean age, 69 years; 18 652 [54%] women) from the KPNC cohort, 93 724 patients (mean age, 61 years; 48 348 [52%] women) from the REDS-III cohort, and 918 996 patients (mean age, 72 years; 522 239 [57%] women) from the SCANDAT cohort. The median number of red blood cell transfusions per patient was 3 in the KPNC cohort, 2 in the REDS-III cohort, and 3 in the SCANDAT cohort. The percentage of transfusions from previously pregnant or parous donors was 9% in the KPNC cohort, 18% in the REDS-III cohort, and 25% in the SCANDAT cohort. The percentage of transfusions in the 3 cohorts from female donors ranged from 39% to 43%, from previously pregnant or parous donors ranged from 9% to 25%, and from sex-discordant donors ranged from 44% to 50%. There were 3217 in-hospital deaths in the KPNC cohort, 8519 in the REDS-III cohort, and 198 537 in the SCANDAT cohort. There were no statistically significant associations between any of the 3 donor exposures and in-hospital mortality in the 3 cohorts. Hazard ratios for in-hospital mortality per transfused unit from female donors were 0.99 (95% CI, 0.96-1.03) for the KPNC cohort, 1.00 (95% CI, 0.99-1.01) for the REDS-III cohort, and 1.00 (95% CI, 0.99-1.00) for the SCANDAT cohort. For units from previously pregnant or parous female donors, hazard ratios were 1.00 (95% CI, 1.00-1.01) for the KPNC cohort, 1.01 (95% CI, 0.98-1.03) for the REDS-III cohort, and 1.00 (95% CI, 1.00-1.01) for the SCANDAT cohort. For units from sex-discordant transfusions, hazard ratios were 1.02 (95% CI, 0.99-1.05) for the KPNC cohort, 0.99 (95% CI, 0.98-1.00) for the REDS-III cohort, and 1.00 (95% CI, 0.99-1.00) for the SCANDAT cohort. Conclusions and Relevance: Among red blood cell transfusion recipients, transfusions from female, previously pregnant, or sex-discordant donors were not significantly associated with increased mortality.

Therapeutic impact of red blood cell transfusion on anemic outpatients: the RETRO study.

BACKGROUND: Patients with cancer or other diagnoses associated with chronic anemia often receive red blood cell (RBC) transfusion as outpatients, but the effect of transfusion on functional status is not well demonstrated. STUDY DESIGN AND METHODS: To estimate the effect of transfusion on functional status and quality of life, we measured 6-minute walk test distance and fatigue- and dyspnea-related quality-of-life scores before and 1 week after RBC transfusion in 208 outpatients age ≥50 with at least one benign or malignant hematology/oncology diagnosis. To account for potential confounding effects of cancer treatment, patients were classified into two groups based on cancer treatment within 4 weeks of the study transfusion. Minimum clinically important improvements over baseline were 20 meters in walk test distance, 3 points in fatigue score, and 2 points in dyspnea score. RESULTS: The median improvement in unadjusted walk test distance was 20 meters overall and 30 meters in patients not receiving recent cancer treatment. Fatigue scores improved overall by a median of 3 points and by 4 points in patients without cancer treatment. There was no clinically important change in dyspnea scores. In multiple linear regression analysis, patients who maintained hemoglobin (Hb) levels of 8 g/dL or greater at 1 week posttransfusion, who had not received recent cancer treatment, and who did not require hospitalization during the study showed clinically important increases in mean walk test distance. CONCLUSIONS: Red blood cell transfusion is associated with a modest, but clinically important improvement in walk test distance and fatigue score outcomes in adult hematology/oncology outpatients.

Genetic analysis of metabolic defects in the spontaneously hypertensive rat.

Abnormalities in carbohydrate and lipid metabolism are common in patients with essential hypertension and in the spontaneously hypertensive rat (SHR). To identify chromosome regions contributing to this clustering of cardiovascular risk factors in the SHR, we searched for quantitative trait loci (QTL) associated with insulin resistance, glucose intolerance, and dyslipidemia by using the HXB/BXH recombinant inbred (RI) strains. Analysis of variance in RI strains suggested significant effects of genetic factors. A genome screening of the RI strains with more than 700 markers revealed QTL significantly associated with insulin resistance on Chromosomes (Chrs) 3 and 19. The Chr 19 QTL was confirmed by testing a previously derived SHR-19 congenic strain: transfer of a Chr 19 segment delineated by markers D19Rat57 and D19Mit7 from the Brown Norway (BN/Cr) strain onto the genetic background of the SHR/Ola was associated with decreased insulin and glucose concentrations and ameliorated insulin resistance at the tissue level. These findings suggest that closely linked genes on Chr 19, or perhaps even a single gene with pleiotropic effects, influence the clustering of metabolic disturbances in the SHR-BN model.