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Ex vivo labeling withAutologous units of whole blood were divided equally into two bags and stored under standard blood bank conditions at 2 to 6°C (N = 4 healthy adult volunteers). One bag was biotinylated (15 μg/ml) on storage days 5 to 7 (fresh) and the other was biotinylated (3 μg/ml) on days 35 to 42 (aged). The proportion of circulating BioRBC was measured serially, and cell-surface biotin was quantified with reference to molecules of equivalent soluble fluorochrome. Clearance kinetics were modeled by RBC age distribution at infusion (Gaussian vs. uniform) and decay over time (constant vs. exponential).Data were consistent with biphasic exponential clearance of cells of uniform age. Our best estimate of BioRBC clearance (half-life [TSimilar clearance kinetics of fresh and aged BioRBC may be due to the extensive washing required during biotinylation. Survival kinetics consistent with cells with uniform rather than Gaussian or other non-uniform age distributions suggest that washing, and potentially RBC culling, may extend the storage life of RBC products.

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.

Sickle cell disease (SCD) patients require urgent red cell exchange (RCE) procedures for acute chest syndrome (ACS), demanding a coordinated effort of multiple clinical services. Execution of RCE is a multistep process from the time the procedure is requested to the time the procedure is initiated. A retrospective review of patients with SCD requiring urgent RCE for ACS and stroke from 2012 to 2017 was performed at a centralized hemapheresis service covering a multihospital healthcare system. A total of 30 urgent RCE procedures performed on 28 patients were evaluated. The time required for red blood cell (RBC) preparation was the longest step in the process (median 3.8 hours). Furthermore, RBC preparation time was longer for sickle cell patients with RBC alloimmunization compared with nonalloimmunized patients (8.6 vs 3.8 hours, P = .03). One mortality event occurred in Ab- group. This study identified potentially modifiable factors, which impact the time to implementation of RCE in one service area. It highlights the importance of a structured and coordinated approach for the efficient and timely delivery of this vital treatment modality.

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 (

Background Some people rapidly develop iron deficiency anemia following blood donation, while others can repeatedly donate without becoming anemic. Methods Two cohorts of blood donors were studied. Participants (775) selected from a 2-year longitudinal study were classified into six analysis groups based on sex, donation intensity, and low hemoglobin deferral. Associations with iron supplement use, cigarette smoking, and four genetic variants of iron metabolism were examined at enrollment and with longitudinal regression models. An unbiased assessment of genetic variability and ability to repeatedly donate blood without experiencing low hemoglobin deferral was conducted on participants (13,403) in a cross-sectional study who were examined by genome wide association (GWA). Results Behaviors and genetic variants were associated with differences in hemoglobin and ferritin change following repeated donation. At least weekly iron supplement use was associated with improved status in first-time donors, while daily use was associated with improved status in high-intensity donors. Cigarette smoking was associated with 0.5 g/dL increased hemoglobin in high-intensity donors. A736V in TMPRSS6 was associated with a rapid drop in hemoglobin and ferritin in first-time females following repeated donation. Conversely, the protective TMPRSS6 genotype was not enriched among high-intensity donors. H63D in HFE was associated with increased hemoglobin in female high-intensity donors. However, no differences in genotype between first-time and high-intensity donors were found in GWA analyses. Conclusion Behavioral and genetic modifiers contributed to first-time donor hemoglobin and iron status, while iron supplement use was more important than underlying genetics in high-intensity donors.

RATIONALE: 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. OBJECTIVES: 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. METHODS: Using flow cytometry and single-cell RNA sequence analyses, we assessed SARS-CoV-2-specific responses in our cohort. MEASUREMENTS AND MAIN RESULTS: 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 (P < 0.0001). In severe disease, immunodominant CD4(+) T-cell responses to Spike-1 (S1) produced increased in vitro TNF-alpha (tumor necrosis factor-alpha) but demonstrated impaired S1-specific proliferation and increased susceptibility to activation-induced cell death after antigen exposure. CD4(+) TNF-alpha(+) T-cell responses inversely correlated with absolute CD4(+) counts from patients with severe COVID-19 (n = 76; R = - 0.797; P < 0.0001). In vitro TNF-alpha 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 (P < 0.001). Single-cell RNA sequencing demonstrated marked downregulation of type-1 cytokines and NFKB 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-alpha compared with peripheral blood mononuclear cells. CONCLUSIONS: Together, our findings show CD4(+) dysfunction in severe COVID-19 is TNF-alpha/TNF receptor 1-dependent through immune mechanisms that may contribute to lymphopenia. TNF-alpha blockade may be beneficial in severe COVID-19.

Background Extrapolation of clinical trial results comparing warfarin and direct-acting oral anticoagulant (DOAC) users experiencing major hemorrhage to clinical care is challenging due to differences seen among non-randomized oral anticoagulant users, bleed location, and etiology. We hypothesized that inpatient all-cause-mortality among patients presenting with major hemorrhage differed based on the home-administered anticoagulant medication class, DOAC versus warfarin. Methods More than 1.5 million hospitalizations were screened and 3731 patients with major hemorrhage were identified in the REDS-III Recipient Database. Propensity score matching and stratification were used to account for potentially confounding factors. Results Inpatient all-cause-mortality was lower for DOAC (HR = 0.60, 95%CI 0.45–0.80, p = 0.0005) before accounting for confounding and competing events. Inpatient all-cause-mortality for 1266 propensity-score-matched patients compared using proportional hazards regression did not differ (HR = 0.84, 95%CI 0.58–1.22, p = 0.36). Inpatient all-cause-mortality in stratified analyses (warfarin as reference) produced: HR = 0.69 (95%CI 0.31–1.55) for traumatic head injuries; HR = 1.10 (95%CI 0.62–1.95) for non-traumatic head injuries; HR = 0.62 (95%CI 0.20–1.94) for traumatic, non-head injuries; and HR = 0.69 (95%CI 0.29–1.63) for non-traumatic, non-head injuries. Mean time to discharge was shorter for DOAC (HR = 1.17, 95%CI 1.05–1.30, p = 0.0034) in the propensity score matched analysis. Plasma transfusion occurred in 42% of warfarin hospitalizations and 11% of DOAC hospitalizations. Vitamin K was administered in 63% of warfarin hospitalizations. Conclusions After accounting for differences in patient characteristics, location of bleed, and traumatic injury, inpatient survival was no different in patients presenting with major hemorrhage while on DOAC or warfarin.

Background Red blood cells (RBCs) can be labeled with N-hydroxysuccinimidobiotin (sulfo-NHS-biotin), which binds to cell surface proteins under aqueous conditions. Biotinylated RBCs can be safely infused and detected in peripheral blood samples using flow cytometry, using a fluorochrome-conjugated streptavidin (SA) detection reagent. Biotinylated RBCs have been used to track survival of transfused RBCs, and have applications in optimizing RBC storage and in understanding donor genetic, environmental and disease factors affecting RBC products. Methods We have developed a closed-system, current good manufacturing practices (cGMP)–compliant procedure for biotinylation of RBCs and a quantitative flow cytometric assay to estimate the dose of cell-bound biotin delivered to the patient. Resulting products were characterized for variability, sterility, endotoxin, hemolysis, total dose of cell-bound biotin and stability. Results The density of biotin-labeling increased as a log-linear function of sulfo-NHS-biotin–labeling concentration, with greater variability at lower concentrations. The upper estimates of biotin doses in the average product (mean RBC content = 5.55 × 1011) were 9.8 and 73.0 µg for products labeled at 3 and 15 µg sulfo-NHS-biotin/mL of total reaction mixture (27 and 135 nmol/mL packed RBCs), respectively. All products were negative for bacterial and fungal growth at 14 days and were below the limit of endotoxin detection. Biotinylated RBCs were stable in vitro for up to 50 days after labeling. Discussion We have validated a closed-system procedure for biotinylating RBCs for investigational use. A standard operating procedure is presented in sufficient detail for implementation in a cGMP-compliant cell-processing facility.

Lymphopenia is common in severe COVID-19 disease, yet the mechanisms are poorly understood. 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 to recovered, mild disease (p+ T cell responses to Spike-1(S1) produced increased in vitro TNF-α, but impaired proliferation and increased susceptibility to activation-induced cell death (AICD). CD4+TNF-α+ T cell responses inversely correlated with absolute CD4+ counts from severe COVID-19 patients (n=76; R=-0.744, P+ proliferation and abrogated S1-AICD in severe COVID-19 patients (P+ cells with infliximab treatment. Lung CD4+ T cells in severe COVID-19 were reduced and produced higher TNF-α versus PBMC. Together, our findings show COVID-19-associated CD4+ lymphopenia and dysfunction is autocrine TNF-α/TNFRI-dependent and therapies targeting TNF-α may be beneficial in severe COVID-19.One Sentence SummaryAutocrine TNF-α/TNFRI regulates CD4+ T cell lymphopenia and dysfunction in severe COVID-19 disease.

Restless legs syndrome (RLS) is a common sensorimotor disorder, which can disrupt sleep and is thought to be caused in part by low cellular iron stores. Proton pump inhibitors (PPI) and histamine H2-receptor antagonists (H2A) are among the most commonly used drugs worldwide and show evidence of causing iron deficiency. We conducted a case/non-case observational study of blood donors in the United States (N = 13,403; REDS-III) and Denmark (N = 50,323; Danish Blood Donor Study, DBDS), both of which had complete blood count measures and a completed RLS assessment via the Cambridge–Hopkins RLS questionnaire. After adjusting for age, sex, race, BMI, blood donation frequency, smoking, hormone use, and iron supplement use, PPI/H2A use was associated with RLS (odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.13–1.76; p = 0.002) in REDS-III for both PPI (OR = 1.43; CI, 1.03–1.95; p = 0.03) and H2A (OR = 1.56; CI, 1.10–2.16; p = 0.01). DBDS exhibited a similar association with PPIs/H2As (OR = 1.29; CI, 1.20–1.40; p < 0.001), and for PPIs alone (OR = 1.27; CI, 1.17–1.38; p < 0.001), but not H2As alone (OR = 1.18; CI, 0.92–1.53; p = 0.2). We found no evidence of blood iron stores mediating this association. The association of PPI, and possibly H2A, consumption with RLS independent of blood iron status and other factors which contribute to RLS risk suggest the need to re-evaluate use of PPI/H2A in populations at particular risk for RLS.

BACKGROUND Consensus guidelines recommend that therapeutic plasma exchange (TPE) should be started within 4 to 8 hours after the diagnosis of suspected acquired thrombotic thrombocytopenic purpura (aTTP). This study aimed to audit the steps from diagnosis to initiation of plasma exchange at a centralized apheresis service. METHODS A retrospective review of the electronic medical record and laboratory information systems from January 1, 2014 to August 31, 2017 was conducted to identify all patients with suspected aTTP undergoing TPE. Demographics, comorbidities, pertinent laboratory tests, and temporal TPE procedural data were collected. RESULTS The median (5th-95th percentile) time from request to initiation of TPE was 5.4 (3.2-10.6) hours. TPE was initiated within 8 hours in 94 of the 108 patients (87.0%). The median (5th-95th percentile) time from request to central venous access was 2.5 (0.5-6.9) hours and from request to plasma product issuance from the blood bank was 3.4 (1.6-8.1) hours. aTTP patients in whom TPE was initiated greater than 6 hours from request did not have worse outcomes compared to those with TPE initiation within 6 hours: in-hospital mortality (2/14 [14.3%] vs 2/21 [9.5%], P = 0.66), median length of stay (9.0 [4.7-44.1] vs 8.3 [3.9-27.0] days, P = 0.76), and median number of days to durable platelet count recovery (4.5 [2.0-9.0] vs 4.0 [2.0-18.0] days, P = 0.66). CONCLUSIONS The 4 to 8-hour target window from TPE request to initiation appears feasible for a centralized apheresis program servicing a large healthcare system.

Previous observational studies suggest associations between red blood cell (RBC) transfusion and risk for arterial or venous thrombosis. We determined the association between thrombosis and RBC transfusion in hospitalized patients using the Recipient Database from the National Heart Lung and Blood Institute (NHLBI) Recipient Epidemiology and Donor Evaluation Study-III. A thrombotic event was a hospitalization with an arterial or venous thrombosis ICD-9 code and administration of a therapeutic anticoagulant or antiplatelet agent. Patients with history of thrombosis or a thrombosis within 24 hours of admission were excluded. A proportional hazards regression model with time-dependent covariates was calculated. Estimates were adjusted for age, sex, hospital, smoking, medical comorbidities, and surgical procedures. Of 657 412 inpatient admissions, 67 176 (10.2%) received at least one RBC transfusion. Two percent (12927) of patients experienced a thrombosis. Of these, 2587 developed thrombosis after RBC transfusion. In unadjusted analyses, RBC transfusion was associated with an increased thrombosis risk [HR = 1.3 (95% CI 1.23-1.36)]. After adjustment for surgical procedures, age, sex, hospital, and comorbidities, no association between RBC transfusion on risk of venous and arterial thrombosis was found [HR 1.0 (95% CI: 0.96-1.05)]. Thus, RBC transfusion does not appear to be an important risk factor for thrombosis in most hospitalized patients.

Background Immunomodulatory strategies in heparin-induced thrombocytopenia (HIT) include the use of intravenous immune globulin (IVIG) and therapeutic plasma exchange (TPE). The optimal application of these therapies is unknown and outcomes data are limited. We investigated treatment categories and laboratory and clinical outcomes of IVIG and/or TPE in HIT with a systematic literature review. Study design and methods We searched MEDLINE, Embase, and Web of Science through December 2019 for studies combining controlled vocabulary and keywords related to thrombocytopenia, heparin, TPE, and IVIG. The primary outcome was treatment indication. Secondary outcomes were platelet recovery, HIT laboratory parameters, heparin re-exposure, and post-treatment course. Case-level data were analyzed by qualitative synthesis. Results After 4241 references were screened, we identified 60 studies with four main categories of IVIG and/or TPE use as follows: (a) treatment of refractory HIT (n = 35; 31%); (b) initial therapy (n = 45; 40%); (c) cardiopulmonary bypass surgery (CPB; n = 30; 27%); and (d) other (n = 2; 2%). IVIG was most commonly used for the treatment of refractory HIT while TPE was primarily used to facilitate heparin exposure during CPB. Both IVIG and TPE were equally used as initial therapy. Heparin re-exposure occurred without thrombotic event in 29 TPE-treated patients and three IVIG-treated patients. Conclusion In patients with HIT, both TPE and IVIG are used for initial therapy or treatment of refractory HIT. However, TPE is more commonly used in patients undergoing CPB. Prospective studies may help clarify which treatment is indicated in HIT population subsets.

Hemostatic abnormalities are common among critically ill patients and are associated with a high risk of bleeding. The abnormalities range from isolated thrombocytopenia or prolongation of global coagulation assays to complex disease states, such as thrombotic microangiopathic syndromes, and can be associated with a wide range of conditions, including trauma, surgery, acute disease processes, cardiopulmonary bypass, and exposure to drugs and blood products. Prompt identification of underlying causes is important because treatment strategies vary. Moreover, prompt initiation of both supportive and specific treatments is vital to decrease the morbidity and mortality in the intensive care unit.

Iron deficiency anemia is a common clinical condition often treated with tablets containing 65 mg of elemental iron. Such doses can elicit gastrointestinal side effects lowering patient compliance. Oral iron supplements also increase hepcidin production causing decreased fractional absorption of subsequent doses. Frequent blood donors often become iron deficient. Therefore, they were enrolled in a two-year study involving continued blood donations and randomization to receive no pill, placebo, 19, or 38 mg ferrous gluconate for 60 days. Total body iron (TBI) did not change for the subset of donors in the no pill and placebo groups who completed both enrollment and final visits (p=0.21 and p=0.28, respectively). However, repeated measures regression analysis on the complete dataset estimated a significant decrease in TBI of 52 mg/year for the placebo and no pill groups (p=0.001). The effects of 19 and 38 mg iron supplementation on TBI were indistinguishable (p=0.54). TBI increased by 229 mg after the initial 60 days of iron supplementation (p

BACKGROUND Repeated blood donation alters the iron balance of blood donors. We quantified these effects by analyzing changes in body iron as well as calculating iron absorbed per day for donors enrolled in a prospective study. STUDY DESIGN AND METHODS For 1308 donors who completed a final study visit, we calculated total body iron at the enrollment and final visits and the change in total body iron over the course of the study. Taking into account iron lost from blood donations during the study and obligate losses, we also calculated the average amount of iron absorbed per day. RESULTS First-time/reactivated donors at enrollment had iron stores comparable to previous general population estimates. Repeat donors had greater donation intensity and greater mean iron losses than first-time/reactivated donors, yet they had little change in total body iron over the study period, whereas first-time/reactivated donors had an average 35% drop. There was higher estimated iron absorption in the repeat donors (men: 4.49 mg/day [95% confidence interval [CI], 4.41-4.58 mg/day]; women: 3.75 mg/day [95% CI, 3.67-3.84 mg/day]) compared with estimated iron absorption in first-time/reactivated donors (men: 2.89 mg/day [95% CI, 2.75-3.04 mg/day]; women: 2.76 mg/day [95% CI, 2.64-2.87 mg/day]). The threshold for negative estimated iron stores (below “0” mg/kg stores) was correlated with the development of anemia at a plasma ferritin value of 10 ng/mL. CONCLUSIONS These analyses provide quantitative data on changes in estimated total body iron for a broad spectrum of blood donors. In contrast to using ferritin alone, this model allows assessment of the iron content of red blood cells and the degree of both iron surplus and depletion over time.

BACKGROUND Upper-extremity transplantation (UET) is a reality. Immunologic, functional, and graft survival outcomes have been encouraging. However, these complex reconstructions have unique considerations that pose distinct challenges. Transplant programs have reported morbidity and mortality due to significant intraoperative blood losses, but similar data are scant during other phases of recovery. We report experience from two centers on complete blood component demands and utilization with UET. STUDY DESIGN AND METHODS Inpatient medical records of UET recipients from intraoperative (time from initiation of transplant surgery to exit from the operative suite) and postoperative (exit from the operative suite to discharge from the hospital) phases were retrospectively reviewed. RESULTS Six patients received various UETs and mean (±SD) postoperative hospital stay was 46 (±14.4) days. Mean (±SD) intraoperative blood unit utilization was 14.8 (±10.2) red blood cells (RBCs), 10.5 (±11.8) plasma, 0.8 (±1.2) platelets (PLTs), and 0.3 (±0.8) cryoprecipitate units. Mean postoperative blood unit utilization was 9.3 (±10.4) RBCs, 5.3 (±6.7) plasma, 1.2 (±2.0) PLTs, and 0.7 (±1.6) cryoprecipitate units. Both intraoperative and postoperative blood utilization for unilateral versus bilateral transplant were different, but not significantly so. However, total inpatient blood use in bilateral transplants was significantly greater than in unilateral transplants. CONCLUSION Substantial blood loss may occur in UET and require transfusion of many blood components, primarily RBCs and plasma. We propose an UET transfusion protocol and suggest that centers preparing to perform these transplants should actively engage the transfusion medicine service to ensure availability and access to appropriate blood components for the entire hospitalizations of these unique patients.

BACKGROUND Pica, the compulsive consumption of ice or other nonnutritious substances, is associated with iron deficiency, a common negative consequence of frequent blood donation. Because of this, blood donors, such as those participating in the Strategies to Reduce Iron Deficiency (STRIDE) study, are an ideal population to explore pica and iron deficiency. STUDY DESIGN AND METHODS STRIDE was a 2-year intervention trial to assess the effectiveness of iron supplementation for mitigating iron deficiency in frequent blood donors. Subjects completed baseline and follow-up questionnaires that included questions about pica symptoms. In-depth telephone interviews were conducted with 14 of these subjects reporting pica symptoms and eight presumed controls (casual ice chewers) to gain a deeper understanding of pica symptoms and their impact on daily life and to make a final determination on the presence of pica. RESULTS Pica was confirmed in five of the 14 subjects reporting symptoms and in two of eight controls. Outcome misclassification based on the questionnaire was attributed to inadequate assessment of several pica symptoms identified during the interview. Comparison of subjects' repeated quantitative iron measurements taken throughout STRIDE with subjects' final adjudicated pica status revealed a positive relationship between development of pica and worsening iron status; the opposite was found in those whose pica symptoms resolved. CONCLUSION Continued refinement of pica symptom questions will allow for rapid and accurate detection of pica in frequent blood donors and confirmation of successful treatment with iron supplements.

INTRODUCTION: Anti-heparin/platelet factor 4 antibody immune complexes resulting from heparin-induced thrombocytopenia (HIT) are removed by therapeutic plasma exchange (TPE). We sought to define TPE in HIT practice patterns using an international survey. METHODS: A 31-item online survey was disseminated through the American Society for Apheresis. After institutional duplicate responses were eliminated, a descriptive analysis was performed. RESULTS: The survey was completed by 94 respondents from 78 institutions in 18 countries. Twenty-nine institutions (37%) used TPE for HIT (YES Cohort) and 49 (63%) did not (NO Cohort). Most NO respondents (65%) cited “no requests received” as the most common reason for not using TPE. Of the 29 YES respondents, 10 (34%) gave incomplete information and were excluded from the final analysis, leaving 19 responses. Of these, 18 (95%) treated ≤ 10 HIT patients over a 2-year period. The most common indications were cardiovascular surgery (CS; 63%) and HIT-associated thrombosis (HT; 26%). The typical plasma volume processed was 1.0 (63% CS and 58% HT). For CS, the typical replacement fluid was plasma (42%) and for HT, it was determined on an individual basis (32%). For CS, patients were treated with a set number of TPE procedures (37%) or laboratory/clinical response (37%). For HT, the number of TPE procedures typically depended on laboratory/clinical response (42%). CONCLUSION: In a minority of responding institutions, TPE is most commonly used in HIT to prophylactically treat patients who will undergo heparin re-exposure during cardiovascular surgery. Prospective studies are needed to more clearly define the role of TPE in HIT.

BACKGROUND: The optimal approach for reducing iron depletion (ID) in blood donors may vary depending on biologic or behavioral differences across donors. STUDY DESIGN AND METHODS: More than 12,600 successful whole blood donors were enrolled from four US blood centers for ferritin testing. The study population was enriched for racial/ethnic minorities (1605 African American, 1616 Asian, 1023 Hispanic). Subjects completed questionnaires on ID risk factors. Logistic regression identified predictors of absent iron stores (AIS; ferritin

BACKGROUND Understanding the effect of delayed processing of whole blood on plasma ferritin will inform the feasibility of both routine ferritin testing in donors and clinical research study design. STUDY DESIGN AND METHODS Whole blood tubes drawn from 16 donors were held at 4°C and centrifuged at 24-hour intervals to assess plasma ferritin concentration up to 5 days after draw. Intraindividual variation over time was measured in 21 healthy donors in blood samples collected weekly for 4 weeks and then at 12 weeks. RESULTS No significant variation in plasma ferritin concentration was observed in blood stored at 4°C for up to 5 days after draw (p = 0.32). The estimated loss of 4.75% ferritin over 5 days was within the reported 5% variation of the assay. Moderate intraindividual variation occurs over time in both sexes, with variability increasing with the mean. No difference was detected between men and women in the regression of standard deviation on mean ferritin (p = 0.43). CONCLUSIONS Ferritin is stable in whole blood up to 5 days, demonstrating operational feasibility of its use in monitoring donor iron stores. Moderate fluctuations over time occur, but ferritin measurements are sufficiently reliable to determine donor iron status on the day of donation.

BACKGROUND Understanding the effect of blood donation and iron supplementation on iron balance will inform strategies to manage donor iron status. STUDY DESIGN AND METHODS A total of 215 donors were randomized to receive ferrous gluconate daily (37.5 mg iron) or no iron for 24 weeks after blood donation. Iron stores were assessed using ferritin and soluble transferrin receptor. Hemoglobin (Hb) iron was calculated from total body Hb. Total body iron (TBI) was estimated by summing iron stores and Hb iron. RESULTS At 24 weeks, TBI in donors taking iron increased by 281.0 mg (95% confidence interval [CI], 223.4-338.6 mg) compared to before donation, while TBI in donors not on iron decreased by 74.1 mg (95% CI, −112.3 to −35.9; p

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.

Background High school students 16 to 18 years-old contribute 10% of the US blood supply. Mitigating iron depletion in these donors is important because they continue to undergo physical and neurocognitive development. Study design and methods Study objectives were to determine the prevalence of iron depletion in 16- to 18-year-old donors and whether their risk for iron depletion was greater than adult donors. Successful, age-eligible donors were enrolled from high school blood drives at two large US blood centers. Plasma ferritin testing was performed with ferritin less than 12 ng/mL as our primary measure of iron depletion and ferritin less than 26 ng/mL a secondary measure. Multivariable repeated-measures logistic regression models evaluated the role of age and other demographic/donation factors. Results Ferritin was measured from 4265 enrollment donations September to November 2015 and 1954 follow-up donations through May 2016. At enrollment, prevalence of ferritin less than 12 ng/mL in teenagers was 1% in males and 18% in females making their first blood donation, and 8% in males and 33% in females with prior donations. Adjusted odds for ferritin less than 12 ng/mL were 2.1 to 2.8 times greater in 16- to 18-year-olds than in 19- to 49-year-olds, and for ferritin less than 26 ng/mL were 3.3- to 4.7-fold higher in 16- to 18-year-olds. Progression to hemoglobin deferral was twice as likely in 16- to 18-year-old versus 19- to 49-year-old females. Conclusion Age 16 to 18 years-old is an independent risk factor for iron deficiency in blood donors at any donation frequency. Blood centers should implement alternate eligibility criteria or additional safety measures to protect teenage donors from iron depletion.

Blood donors and the RBCs and other components they willingly provide are essential in the delivery of healthcare in all parts of the world. Nearly 70% of donated blood comes from repeat or committed donors. The amount of iron removed in the 10 min or so it takes to withdraw a unit of blood (500 ml, plus 25 ml for testing) requires over 24 weeks to replace on a "standard" diet, i.e., without added iron in the form of supplements The cumulative effect of repeat blood donations without adequate iron replacement or a longer wait between donations results in iron deficiency (ID) in many donors, low haemoglobin deferral (~8% of donation attempts), and frank anaemia in some. Moreover, ID can be associated with side effects that can impact a blood donor's health, such as fatigue, cognitive changes and other neuromuscular symptoms. In an effort to better identify and prevent ID, blood collection agencies are recommending various strategies, including changes in the donation interval, donation frequency, testing of iron status and iron supplementation. In this review, we present the evidence basis for these strategies and suggest our own approaches to improving iron balance in blood donors.

BACKGROUND Currently, low titer A plasma is used on a routine basis in bleeding trauma patients of unknown AB type. Three AB non-bleeding apheresis patients are presented here who safely received a combination of AB and low titer A plasma during therapeutic plasma exchange (TPE). One control AB patient received AB plasma only. METHODS Data was obtained retrospectively on number of procedures, volume replaced, total plasma, and A plasma volumes including hemolysis laboratory data. Average A plasma volume and % of A plasma out of total plasma volume used were calculated. RESULTS Two female AB patients were treated for thrombotic thrombocytopenic purpura (TTP) with TPE and a third female AB patient was treated for microangiopathic hemolytic anemia. Patient 1 received a total of 12 procedures, 10/12 with AB+A plasma (average 916.3 ±84.6 mL). Patient 2 received a total of 12 procedures, 4/12 with AB+A plasma (average 1210.5 ±27.9 mL). Patient 3 received a total of six procedures, four out of six procedures with AB+A plasma (average 1009.8 ±80.3 mL). Patient 4, control, received AB plasma only. Percent of A plasma volume exchanged ranged between 23.8% and 47.8%. Haptoglobin, LDH, hemoglobin, and total bilirubin were monitored and trends were comparable with the control patient. The patients had a negative follow up direct antiglobulin test, adequate platelet recovery and a favorable clinical outcome with treatments. CONCLUSIONS TPE was effectively performed without evidence of increased hemolysis using up to 47.8% of low titer A plasma. This approach can reduce strains on limited supplies of AB plasma whereas providing a vital treatment alternative for AB patients undergoing TPE with plasma replacement.

BACKGROUND The historical approach of offering dietary advice to donors with low hemoglobin (Hb) is ineffective for preventing iron deficiency in frequent donors. Alternative approaches to maintaining donor iron status were explored. STUDY DESIGN AND METHODS Frequent blood donors were randomly assigned into five arms for 2 years of follow-up. Three double-blinded arms provided 60 once-daily pills after each donation (38, 19, or 0 mg of iron). Two single-blinded arms provided iron status (ferritin) or no information letters after each donation. Ferritin, soluble transferrin receptor, and complete blood count were measured at each donation. RESULTS There were 692 subjects enrolled and 393 completed the study. Subjects in pill groups deenrolled more than those in letter groups (39% vs. 7%). Adverse events occurred equally in subjects receiving iron or placebo pills. Of those completing the study, the prevalence of ferritin of less than 12 or less than 26 ng/mL declined by more than 50% and was statistically indistinguishable in the three intervention groups (19 or 38 mg of iron; iron status letter). Longitudinal analyses of all subjects showed improved iron status in iron pill groups and worsening iron status in control groups (placebo; no information letter). The iron pill groups experienced a net increase of approximately 0.6 g/dL Hb compared to control groups. The iron status letter group had little change in Hb. CONCLUSION Providing 19 or 38 mg of daily iron or iron status information were effective and mostly equivalent interventions for mitigating iron deficiency in regular donors when compared at the end of the 2-year longitudinal phase of the study. Donors without intervention had worsened iron deficiency with continued donation.

High-dose granulocyte transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count500/μL) and proven/probable/presumed infection. Subjects were randomized to receive either (1) standard antimicrobial therapy or (2) standard antimicrobial therapy plus daily granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. The primary end point was a composite of survival plus microbial response, at 42 days after randomization. Microbial response was determined by a blinded adjudication panel. Fifty-six subjects were randomized to the granulocyte arm and 58 to the control arm. Transfused subjects received a median of 5 transfusions. Mean transfusion dose was 54.9 × 10(9) granulocytes. Overall success rates were 42% and 43% for the granulocyte and control groups, respectively (P.99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per transfusion of ≥0.6 × 10(9) granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of granulocyte transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393.

Background An autologous vaccine of apoptotic tumor cells (ATCs) and dendritic cells (DCs) was administered to patients with stage III/IV head and neck squamous cell carcinoma (HNSCC) to study safety and feasibility. Methods Autologous DCs were generated from monocytes, loaded with ATCs, and delivered intranodally. Delayed-type hypersensitivity (DTH) and immunological endpoints were measured prevaccination and postvaccination. Clinical follow-up was required. Results Tumors obtained from 30 patients yielded 2 × 106 to 2 × 108 tumor cells. Only 19 of 30 (63%) were sterile. Ten of 30 patients (33%) had ≥1 × 107 sterile tumor cells required for vaccine production. Eight of 10 patients had positive recall DTH. Five of 10 patients were leukapheresed to generate DCs. Four of 5 patients were vaccinated. ATC-reactive T cells were detected in 3 of 4 patients. All 4 patients survived >5 years. The trial failed to enroll the projected 12 patients and was terminated. Conclusion This vaccine was safe and immunogenic but feasible only in patients with HNSCC with positive prevaccine DTH and ≥1 × 107 sterile tumor cells. All vaccinated patients were long-term disease-free survivors. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

Variations in cord blood manufacturing and administration are common, and the optimal practice is not known. We compared processing and banking practices at 16 public cord blood banks (CBB) in the United States and assessed transplantation outcomes on 530 single umbilical cord blood (UCB) myeloablative transplantations for hematologic malignancies facilitated by these banks. UCB banking practices were separated into 3 mutually exclusive groups based on whether processing was automated or manual, units were plasma and red blood cell reduced, or buffy coat production method or plasma reduced. Compared with the automated processing system for units, the day 28 neutrophil recovery was significantly lower after transplantation of units that were manually processed and plasma reduced (red cell replete) (odds ratio, .19; P = .001) or plasma and red cell reduced (odds ratio, .54; P = .05). Day 100 survival did not differ by CBB. However, day 100 survival was better with units that were thawed with the dextran-albumin wash method compared with the "no wash" or "dilution only" techniques (odds ratio, 1.82; P = .04). In conclusion, CBB processing has no significant effect on early (day 100) survival despite differences in kinetics of neutrophil recovery.

BACKGROUND Donor behaviors in STRIDE (Strategies to Reduce Iron Deficiency), a trial to reduce iron deficiency, were examined. STUDY DESIGN AND METHODS Six hundred ninety-two frequent donors were randomized to receive either 19 or 38 mg iron for 60 days or an educational letter based on their predonation ferritin. Compliance with assigned pills, response to written recommendations, change in donation frequency, and future willingness to take iron supplements were examined. RESULTS Donors who were randomized to receive iron pills had increased red blood cell donations and decreased hemoglobin deferrals compared with controls or with pre-STRIDE donations. Donors who were randomized to receive educational letters had fewer hemoglobin deferrals compared with controls. Of those who received a letter advising of low ferritin levels with recommendations to take iron supplements or delay future donations, 57% reported that they initiated iron supplementation, which was five times as many as those who received letters lacking a specific recommendation. The proportion reporting delayed donation was not statistically different (32% vs. 20%). Of donors who were assigned pills, 58% reported taking them “frequently,” and forgetting was the primary reason for non-compliance. Approximately 80% of participants indicated that they would take iron supplements if provided by the center. CONCLUSIONS Donors who were assigned iron pills had acceptable compliance, producing increased red blood cell donations and decreased low hemoglobin deferrals compared with controls or with pre-STRIDE rates. The majority of donors assigned to an educational letter took action after receiving a low ferritin result, with more donors choosing to take iron than delay donation. Providing donors with information on iron status with personalized recommendations was an effective alternative to directly providing iron supplements.

Background and Objectives Repeated blood donation produces iron deficiency. Changes in dietary iron intake do not prevent donation-induced iron deficiency. Prolonging the interdonation interval or using oral iron supplements can mitigate donation-induced iron deficiency. The most effective operational methods for reducing iron deficiency in donors are unknown. Materials and Methods ‘Strategies To Reduce Iron Deficiency’ (STRIDE) was a two-year, randomized, placebo-controlled study in blood donors. 692 donors were randomized into one of two educational groups or one of three interventional groups. Donors randomized to educational groups either received letters thanking them for donating, or, suggesting iron supplements or delayed donation if they had low ferritin. Donors randomized to interventional groups either received placebo, 19-mg or 38-mg iron pills. Results Iron deficient erythropoiesis was present in 52·7% of males and 74·6% of females at enrolment. Adverse events within 60 days of enrolment were primarily mild gastrointestinal symptoms (64%). The incidence of de-enrolment within 60 days was more common in the interventional groups than in the educational groups (P = 0·002), but not more common in those receiving iron than placebo (P = 0·68). Conclusion The prevalence of iron deficient erythropoiesis in donors enrolled in the STRIDE study is comparable to previously described cohorts of regular blood donors. De-enrolment within 60 days was higher for donors receiving tablets, although no more common in donors receiving iron than placebo.

Apheresis can remove pathogens and mediators that contribute to pathogenic inflammatory responses in diseases not generally considered to be "Hematologic." Erythrocytapheresis can remove intracellular pathogens such as Babesiosis. Plasmapheresis can remove mediators of the inflammatory response in conditions such as sepsis, chronic autoimmune urticaria and malignant pertussis. Leukapheresis can remove potentially harmful leukocytes in Crohn's Disease and malignant pertussis. While apheresis can remove all of these substances, the clinical efficacy and pathophysiologic changes that occur during apheresis in these conditions are largely unknown. Hence, the clinical utility of apheresis in these conditions is largely unknown and research in these areas has the potential to benefit many patients with a variety of diseases.

The American Society for Apheresis (ASFA) conducted a 1 day consensus conference on Thrombotic Thrombocytopenic Purpura (TTP) during its annual meeting in Atlanta, GA, on April 10, 2012. The authors of this article, a subcommittee of ASFA's Clinical Applications Committee, developed several questions with regard to definitions, classification, pathophysiology, diagnosis, management, and future research in TTP. These questions were provided to the seven invited speakers who are the experts in the field of TTP. Two moderators conducted the proceedings of the conference which was attended by more than 100 participants. After each presentation, there was an open discussion that included moderator-selected written questions submitted by the audience. A medical writer-generated transcript of the proceedings as well as each presentation was made available to the authors. Each summary was reviewed and approved by the respective speaker before submission of this article. The subcommittee also developed seven key questions for blinded, electronic polling conducted by the moderators to generate a consensus amongst the speakers. This article includes these presentation summaries as well as results of the electronic poll.

Background: Idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare yet potentially fatal thrombotic microangiopathy. Severe deficiency of ADAMTS13 activity via autoantibody formation has been associated with idiopathic TTP; however, specific triggers are poorly defined. Previous studies have reported seasonal associations of TTP, with warm-weather seasons appearing to have the strongest predilection. We characterized the seasonal distribution of severe ADAMTS13 deficient idiopathic TTP at our multi-hospital institution. Methods: Apheresis records from 2005–2012 were queried for patients with a clinical diagnosis of TTP, accompanying pre-plasmapheresis ADAMTS13 activity

Background The association of blood donation–related iron deficiency with pica or restless legs syndrome (RLS) remains poorly elucidated. This study evaluated the prevalence of RLS and pica in blood donors completing the REDS-II Iron Status Evaluation (RISE) study. Study Design and Methods RISE enrolled 2425 blood donors in a prospective cohort study; 1334 donors provided blood samples to characterize iron status and answered a questionnaire inquiring into symptoms of RLS and pica at a final visit after 15 to 24 months of follow-up. Associations between both conditions and iron status were evaluated. Results There were 9 and 20% of donors reporting symptoms of probable or probable/possible RLS, respectively. Iron depletion and donation intensity were not predictive of RLS. Pica was reported by 65 donors (5.5%), half of whom reported daily cravings. Prevalence of pica increased with degree of iron depletion in women (2% in iron-replete females, 13% in those with ferritin < 12 ng/mL), but not in men. Probable RLS and pica coexpressed in eight individuals, but no more frequently than expected by chance. Conclusion RLS and pica have been associated with iron deficiency in nondonor populations. This study indicates a potentially high prevalence of RLS in frequent blood donors but shows no association with iron status or donation intensity. Low iron stores were associated with higher prevalence of pica, but only in females. Furthermore, the results are incompatible with RLS and pica sharing a common pathophysiology.

Immune thrombocytopenic purpura (ITP) is an autoimmune disease in which IgG-coated platelets are removed from circulation by the spleen, and platelet production is impaired due to increased thrombopoietin (TPO) clearance. Romiplostim, a novel TPO-mimetic agent, is approved for patients with ITP that are unresponsive to traditional treatments. However, there is little experience when using this drug before splenectomy. We describe herein the case of a young female with chronic ITP who was treated with romiplostim, underwent splenectomy shortly thereafter, and required plateletpheresis for postoperative rebound thrombocytosis with concomitant neurologic symptoms. J. Clin. Apheresis 28:321–324, 2013. © 2013 Wiley Periodicals, Inc.

To minimize maintenance immunosuppression in upper-extremity transplantation to favor the risk-benefit balance of this procedure.Despite favorable outcomes, broad clinical application of reconstructive transplantation is limited by the risks and side effects of multidrug immunosuppression. We present our experience with upper-extremity transplantation under a novel, donor bone marrow (BM) cell-based treatment protocol ("Pittsburgh protocol").Between March 2009 and September 2010, 5 patients received a bilateral hand (n = 2), a bilateral hand/forearm (n = 1), or a unilateral (n = 2) hand transplant. Patients were treated with alemtuzumab and methylprednisolone for induction, followed by tacrolimus monotherapy. On day 14, patients received an infusion of donor BM cells isolated from 9 vertebral bodies. Comprehensive follow-up included functional evaluation, imaging, and immunomonitoring.All patients are maintained on tacrolimus monotherapy with trough levels ranging between 4 and 12 ng/mL. Skin rejections were infrequent and reversible. Patients demonstrated sustained improvements in motor function and sensory return correlating with time after transplantation and level of amputation. Side effects included transient increase in serum creatinine, hyperglycemia managed with oral hypoglycemics, minor wound infection, and hyperuricemia but no infections. Immunomonitoring revealed transient moderate levels of donor-specific antibodies, adequate immunocompetence, and no peripheral blood chimerism. Imaging demonstrated patent vessels with only mild luminal narrowing/occlusion in 1 case. Protocol skin biopsies showed absent or minimal perivascular cellular infiltrates.Our data suggest that this BM cell-based treatment protocol is safe, is well tolerated, and allows upper-extremity transplantation using low-dose tacrolimus monotherapy.

Pica, the compulsive consumption of ice or other nonnutritious substances, is associated with iron deficiency, a common negative consequence of frequent blood donation. Because of this, blood donors, such as those participating in the Strategies to Reduce Iron Deficiency (STRIDE) study, are an ideal population to explore pica and iron deficiency.STRIDE was a 2-year intervention trial to assess the effectiveness of iron supplementation for mitigating iron deficiency in frequent blood donors. Subjects completed baseline and follow-up questionnaires that included questions about pica symptoms. In-depth telephone interviews were conducted with 14 of these subjects reporting pica symptoms and eight presumed controls (casual ice chewers) to gain a deeper understanding of pica symptoms and their impact on daily life and to make a final determination on the presence of pica.Pica was confirmed in five of the 14 subjects reporting symptoms and in two of eight controls. Outcome misclassification based on the questionnaire was attributed to inadequate assessment of several pica symptoms identified during the interview. Comparison of subjects' repeated quantitative iron measurements taken throughout STRIDE with subjects' final adjudicated pica status revealed a positive relationship between development of pica and worsening iron status; the opposite was found in those whose pica symptoms resolved.Continued refinement of pica symptom questions will allow for rapid and accurate detection of pica in frequent blood donors and confirmation of successful treatment with iron supplements.

Repeated blood donation alters the iron balance of blood donors. We quantified these effects by analyzing changes in body iron as well as calculating iron absorbed per day for donors enrolled in a prospective study.For 1308 donors who completed a final study visit, we calculated total body iron at the enrollment and final visits and the change in total body iron over the course of the study. Taking into account iron lost from blood donations during the study and obligate losses, we also calculated the average amount of iron absorbed per day.First-time/reactivated donors at enrollment had iron stores comparable to previous general population estimates. Repeat donors had greater donation intensity and greater mean iron losses than first-time/reactivated donors, yet they had little change in total body iron over the study period, whereas first-time/reactivated donors had an average 35% drop. There was higher estimated iron absorption in the repeat donors (men: 4.49 mg/day [95% confidence interval [CI], 4.41-4.58 mg/day]; women: 3.75 mg/day [95% CI, 3.67-3.84 mg/day]) compared with estimated iron absorption in first-time/reactivated donors (men: 2.89 mg/day [95% CI, 2.75-3.04 mg/day]; women: 2.76 mg/day [95% CI, 2.64-2.87 mg/day]). The threshold for negative estimated iron stores (below "0" mg/kg stores) was correlated with the development of anemia at a plasma ferritin value of 10 ng/mL.These analyses provide quantitative data on changes in estimated total body iron for a broad spectrum of blood donors. In contrast to using ferritin alone, this model allows assessment of the iron content of red blood cells and the degree of both iron surplus and depletion over time.

Upper-extremity transplantation (UET) is a reality. Immunologic, functional, and graft survival outcomes have been encouraging. However, these complex reconstructions have unique considerations that pose distinct challenges. Transplant programs have reported morbidity and mortality due to significant intraoperative blood losses, but similar data are scant during other phases of recovery. We report experience from two centers on complete blood component demands and utilization with UET.Inpatient medical records of UET recipients from intraoperative (time from initiation of transplant surgery to exit from the operative suite) and postoperative (exit from the operative suite to discharge from the hospital) phases were retrospectively reviewed.Six patients received various UETs and mean (±SD) postoperative hospital stay was 46 (±14.4) days. Mean (±SD) intraoperative blood unit utilization was 14.8 (±10.2) red blood cells (RBCs), 10.5 (±11.8) plasma, 0.8 (±1.2) platelets (PLTs), and 0.3 (±0.8) cryoprecipitate units. Mean postoperative blood unit utilization was 9.3 (±10.4) RBCs, 5.3 (±6.7) plasma, 1.2 (±2.0) PLTs, and 0.7 (±1.6) cryoprecipitate units. Both intraoperative and postoperative blood utilization for unilateral versus bilateral transplant were different, but not significantly so. However, total inpatient blood use in bilateral transplants was significantly greater than in unilateral transplants.Substantial blood loss may occur in UET and require transfusion of many blood components, primarily RBCs and plasma. We propose an UET transfusion protocol and suggest that centers preparing to perform these transplants should actively engage the transfusion medicine service to ensure availability and access to appropriate blood components for the entire hospitalizations of these unique patients.

Understanding the effect of delayed processing of whole blood on plasma ferritin will inform the feasibility of both routine ferritin testing in donors and clinical research study design.Whole blood tubes drawn from 16 donors were held at 4°C and centrifuged at 24-hour intervals to assess plasma ferritin concentration up to 5 days after draw. Intraindividual variation over time was measured in 21 healthy donors in blood samples collected weekly for 4 weeks and then at 12 weeks.No significant variation in plasma ferritin concentration was observed in blood stored at 4°C for up to 5 days after draw (p = 0.32). The estimated loss of 4.75% ferritin over 5 days was within the reported 5% variation of the assay. Moderate intraindividual variation occurs over time in both sexes, with variability increasing with the mean. No difference was detected between men and women in the regression of standard deviation on mean ferritin (p = 0.43).Ferritin is stable in whole blood up to 5 days, demonstrating operational feasibility of its use in monitoring donor iron stores. Moderate fluctuations over time occur, but ferritin measurements are sufficiently reliable to determine donor iron status on the day of donation.