Background
Due to unique technical challenges, effective peripheral blood stem cell collections (PBSCs) have not been consistently reported in patients weighing less than 5 kg. We describe three ...PBSCs performed in a 4.6‐kg child undergoing myeloablative chemotherapy for high‐grade glioma.
Study Design and Methods
A multidisciplinary group representing the clinical and apheresis teams adapted a PBSC protocol to accommodate the patient's size and collection targets. Special considerations included timing of the collection relative to chemotherapy, vascular access, strategies for monitoring adverse events during collection, and contingencies.
Results and Discussion
The patient underwent three PBSC procedures over 2 days due to suboptimal collection after the first two procedures. For procedure 1, a conservative inlet: anticoagulant (AC) ratio and AC infusion rate of 15 and 0.6 mL/min/L total blood volume (TBV) resulted in premature discontinuation due to clotting. A ratio of 8 and AC infusion rate of 1.5–1.7 mL/min/L TBV with subsequent titration to higher levels were adopted for the second and third procedures. These changes resulted in greater acid‐citrate‐dextrose exposure, that was managed by continuous calcium chloride infusion. There was no hypocalcemia, hypotension, or distress during any procedure. A total of 15 × 106 CD34+ cells/kg were collected. This retrospective review illustrates that PBSC can be safely undertaken in children weighing less than 5 kg.
Whole blood donation rapidly removes approximately 10% of a donor's blood volume and stimulates substantial changes in iron metabolism and erythropoiesis. We sought to identify donors who benefit ...from iron supplementation, describe the nature of the benefit, and define the time course for recovery from donation. Blood samples were collected over 24 weeks following whole blood donation from 193 participants, with 96 participants randomized to 37.5 mg daily oral iron. Changes in total body, red blood cell (RBC), and storage iron, hepcidin, erythropoietin, and reticulocyte count were modeled using semiparametric curves in a mixed model. and the changes were compared among six groups defined by baseline ferritin (<12; 12‐50; ≥50 ng/mL) and iron supplementation. The effect of oral iron on storage and RBC iron recovery was minimal in donors with baseline ferritin ≥50 ng/mL, but sizeable when ferritin was <50 ng/mL. Iron initially absorbed went to RBC and storage iron pools when ferritin was <12 ng/mL but went mostly to RBCs when ferritin was ≥12 ng/mL. Donors with ferritin ≥12 ng/mL had a “ripple” increase in reticulocytes ~100 days after donation indicating physiological responses occur months following donation. Thus, iron supplements markedly enhance recovery from whole blood donation in donors with ferritin <50 ng/mL. However, full recovery from donation requires over 100 days when taking iron. The findings also highlight the value of the study of blood donors for understanding human hemoglobin and iron metabolism and their usefulness for future studies as additional biomarkers are discovered.
BACKGROUND: Regular blood donors are at risk of iron deficiency, but characteristics that predispose to this condition are poorly defined.
STUDY DESIGN AND METHODS: A total of 2425 red blood cell ...donors, either first‐time (FT) or reactivated donors (no donations for 2 years) or frequent donors, were recruited for follow‐up. At enrollment, ferritin, soluble transferrin receptor (sTfR), and hemoglobin were determined. Donor variables included demographics, smoking, dietary intake, use of iron supplements, and menstrual and/or pregnancy history. Models to predict two measures of iron deficiency were developed: Absent iron stores (AIS) were indicated by a ferritin level of less than 12 ng/mL and iron‐deficient erythropoiesis (IDE) by a log(sTfR/ferritin) value of 2.07 or greater.
RESULTS: A total of 15.0% of donors had AIS and 41.7% IDE. In frequent donors, 16.4 and 48.7% of males had AIS and IDE, respectively, with corresponding proportions of 27.1 and 66.1% for females. Donation intensity was most closely associated with AIS and/or IDE (odds ratios from 5.3 to 52.2 for different donation intensity compared to FT donors). Being female, younger, and/or menstruating also increased the likelihood of having AIS and/or IDE, as did having a lower weight. Marginally significant variables for AIS and/or IDE were being a nonsmoker, previous pregnancy, and not taking iron supplements. Dietary variables were in general unrelated to AIS and/or IDE, as was race and/or ethnicity.
CONCLUSION: A large proportion of both female and male frequent blood donors have iron depletion. Donation intensity, sex and/or menstrual status, weight, and age are important independent predictors of AIS and/or IDE. Reducing the frequency of blood donation is likely to reduce the prevalence of iron deficiency among blood donors, as might implementing routine iron supplementation.
Background
Red blood cells (RBCs) derived from patients who receive testosterone replacement therapy (TRT) may be considered eligible for component production and transfusion. The aim of this study ...was to identify testosterone‐dependent changes in RBC metabolism and to evaluate its impact on susceptibility to hemolysis during cold storage.
Study Design and Methods
We characterized stored RBCs from two cohorts of TRT patients who were matched with control donors (no TRT) based upon sex, age, and ethnicity. We further evaluated the impact of testosterone deficiency (orchiectomy) on RBC metabolism in FVB/NJ mice. RBC metabolites were quantified by ultra‐high‐pressure liquid chromatography‐mass spectrometry. RBC storage stability was determined in RBC units from TRT and controls by quantifying storage, osmotic, and oxidative hemolysis.
Results
Orchiectomy in mice was associated with significant (P < 0.05) changes in RBC metabolism as compared with intact males including increased levels of acyl‐carnitines, long‐chain fatty acids (eg, docosapentaenoic acids), arginine, and dopamine. Stored RBCs from TRT patients exhibited higher levels of pentose phosphate pathway metabolites, glutathione, and oxidized purines (eg, hypoxanthine), suggestive of increased activation of antioxidant pathways in this group. Further analyses indicated significant changes in free fatty acids and acyl‐carnitines in response to testosterone therapies. With regard to hemolysis, TRT was associated with enhanced susceptibility to osmotic hemolysis. Correlation analyses identified acyl‐carnitines as significant modifiers of RBC predisposition to osmotic and oxidative hemolysis.
Conclusions
These observations provide new insights into testosterone‐mediated changes in RBC metabolome and biology that may impact the storage capacity and posttransfusion efficacy of RBCs from TRT donors.
Lymphopenia is common in severe coronavirus disease (COVID-19), yet the immune mechanisms are poorly understood. As inflammatory cytokines are increased in severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2) infection, we hypothesized a role in contributing to reduced T-cell numbers.
We sought to characterize the functional SARS-CoV-2 T-cell responses in patients with severe versus recovered, mild COVID-19 to determine whether differences were detectable.
Using flow cytometry and single-cell RNA sequence analyses, we assessed SARS-CoV-2-specific responses in our cohort.
In 148 patients with severe COVID-19, we found lymphopenia was associated with worse survival. CD4
lymphopenia predominated, with lower CD4
/CD8
ratios in severe COVID-19 compared with patients with mild disease (
< 0.0001). In severe disease, immunodominant CD4
T-cell responses to Spike-1 (S1) produced increased
TNF-α (tumor necrosis factor-α) but demonstrated impaired S1-specific proliferation and increased susceptibility to activation-induced cell death after antigen exposure. CD4
TNF-α
T-cell responses inversely correlated with absolute CD4
counts from patients with severe COVID-19 (
= 76;
= -0.797;
< 0.0001).
TNF-α blockade, including infliximab or anti-TNF receptor 1 antibodies, strikingly rescued S1-specific CD4
T-cell proliferation and abrogated S1-specific activation-induced cell death in peripheral blood mononuclear cells from patients with severe COVID-19 (
< 0.001). Single-cell RNA sequencing demonstrated marked downregulation of type-1 cytokines and NFκB signaling in S1-stimulated CD4
cells with infliximab treatment. We also evaluated BAL and lung explant CD4
T cells recovered from patients with severe COVID-19 and observed that lung T cells produced higher TNF-α compared with peripheral blood mononuclear cells.
Together, our findings show CD4
dysfunction in severe COVID-19 is TNF-α/TNF receptor 1-dependent through immune mechanisms that may contribute to lymphopenia. TNF-α blockade may be beneficial in severe COVID-19.
BACKGROUND: Blood donors are at risk of iron deficiency. We evaluated the effects of blood donation intensity on iron and hemoglobin (Hb) in a prospective study.
STUDY DESIGN AND METHODS: Four ...cohorts of frequent and first‐time or reactivated (FT/RA) blood donors (no donation in 2 years), female and male, totaling 2425, were characterized and followed as they donated blood frequently. At enrollment and the final visit, ferritin, soluble transferrin receptor (sTfR), and Hb were determined. Models to predict iron deficiency and Hb deferral were developed. Iron depletion was defined at two levels: iron deficiency erythropoiesis (IDE) log(sTfR/ferritin) ≥ 2.07 and absent iron stores (AIS; ferritin < 12 ng/mL).
RESULTS: Among returning female FT and RA donors, 20 and 51% had AIS and IDE at their final visit, respectively; corresponding proportions for males were 8 and 20%. Among female frequent donors who returned, 27 and 62% had AIS and IDE, respectively, while corresponding proportions for males were 18 and 47%. Predictors of IDE and/or AIS included a higher frequency of blood donation in the past 2 years, a shorter interdonation interval, and being female and young; conversely, taking iron supplements reduced the risk of iron depletion. Predictors of Hb deferral included female sex, black race, and a shorter interdonation interval.
CONCLUSIONS: There is a high prevalence of iron depletion in frequent blood donors. Increasing the interdonation interval would reduce the prevalence of iron depletion and Hb deferral. Alternatively, replacement with iron supplements may allow frequent donation without the adverse outcome of iron depletion.
BACKGROUND
Frequent whole blood donations increase the prevalence of iron depletion in blood donors, which may subsequently interfere with normal erythropoiesis. The purpose of this study was to ...evaluate the associations between donation frequency and red blood cell (RBC) storage stability in a racially/ethnically diverse population of blood donors.
STUDY DESIGN
Leukoreduced RBC concentrate–derived samples from 13,403 donors were stored for 39 to 42 days (1–6°C) and then evaluated for storage, osmotic, and oxidative hemolysis. Iron status was evaluated by plasma ferritin measurement and self‐reported intake of iron supplements. Donation history in the prior 2 years was obtained for each subject.
RESULTS
Frequent blood donors enrolled in this study were likely to be white, male, and of older age (56.1 ± 5.0 years). Prior donation intensity was negatively associated with oxidative hemolysis (p < 0.0001) in multivariate analyses correcting for age, sex, and race/ethnicity. Increased plasma ferritin concentration was associated with increased RBC susceptibility to each of the three measures of hemolysis (p < 0.0001 for all), whereas self‐reported iron intake was associated with reduced susceptibility to osmotic and oxidative hemolysis (p < 0.0001 for both).
CONCLUSIONS
Frequent blood donations may alter the quality of blood components by modulating RBC predisposition to hemolysis. RBCs collected from frequent donors with low ferritin have altered susceptibility to hemolysis. Thus, frequent donation and associated iron loss may alter the quality of stored RBC components collected from iron‐deficient donors. Further investigation is necessary to assess posttransfusion safety and efficacy in patients receiving these RBC products.
BACKGROUND
The Red Blood Cell (RBC)‐Omics study was initiated to build a large data set containing behavioral, genetic, and biochemical characteristics of blood donors with linkage to outcomes of the ...patients transfused with their donated RBCs.
STUDY DESIGN AND METHODS
The cohort was recruited from four US blood centers. Demographic and donation data were obtained from center records. A questionnaire to assess pica, restless leg syndrome, iron supplementation, hormone use, and menstrual and pregnancy history was completed at enrollment. Blood was obtained for a complete blood count, DNA, and ferritin testing. A leukocyte‐reduced RBC sample was transferred to a custom storage bag for hemolysis testing at Storage Days 39 to 42. A subset was recalled to evaluate the kinetics and stability of hemolysis measures.
RESULTS
A total of 13,403 racially/ethnically diverse (12% African American, 12% Asian, 8% Hispanic, 64% white, and 5% multiracial/other) donors of both sexes were enrolled and ranged from 18 to 90 years of age; 15% were high‐intensity donors (nine or more donations in the prior 24 mo without low hemoglobin deferral). Data elements are available for 97% to 99% of the cohort.
CONCLUSIONS
The cohort provides demographic, behavioral, biochemical, and genetic data for a broad range of blood donor studies related to iron metabolism, adverse consequences of iron deficiency, and differential hemolysis (including oxidative and osmotic stress perturbations) during RBC storage. Linkage to recipient outcomes may permit analysis of how donor characteristics affect transfusion efficacy. Repository DNA, plasma, and RBC samples should expand the usefulness of the current data set.
See article on page 2–5, in this issue
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