Stored platelet hemostatic phenotype and function is not altered when donors are on testosterone replacement therapy.

BACKGROUND: Critical shortages in the national blood supply have led to a re-evaluation of previously overlooked donor sources for blood products. As a part of that effort, red blood cells collected from therapeutic phlebotomy of donors on testosterone replacement therapy (TRT) have been conditionally approved for transfusion. However, platelets from TRT donors are not currently approved for use due to limited data on effects of supraphysiologic testosterone on recipient safety and platelet function. The objective of this study was to provide a comprehensive profile of phenotype and function in platelets from TRT and control donors. STUDY DESIGN AND METHODS: Platelets in plasma were collected from TRT and control donors (N = 10 per group; age- and sex-matched) and stored at room temperature for 7 days. On storage Day 1 (D1) and Day 7 (D7), platelet products were analyzed for platelet count, metabolic parameters (i.e., glucose, lactate, mitochondrial function), surface receptor expression, aggregation, thrombin generation, and thrombus formation under physiological flow conditions. RESULTS: TRT donor platelets were not significantly different than control donor platelets in terms of count, surface phenotype, metabolic function, ability to aggregate, thrombin generation, or ability to form occlusive thrombus under arterial flow regimes. Both groups were similar to each other by D7, but had significantly lost hemostatic function compared to D1. DISCUSSION: Platelets derived from donors undergoing TRT have similar phenotypic and functional profiles compared to those derived from control donors. This suggests that therapeutic phlebotomy of TRT donors may provide a useful source for platelet products.

Biotin labeling allows for post-transfusion functional assessment of stored human platelets in mice.

BACKGROUND: Platelet radiolabeling with radioisotopes is currently used for human platelet recovery and survival studies. Biotinylation enables ex vivo post-transfusion platelet function testing. Whether platelet biotinylation itself affects platelet function is controversial. STUDY DESIGN AND METHODS: Platelet concentrates from healthy humans were stored for 6 days. Samples were obtained at 1 or 2 and 6 days, and platelets were labeled following a radiolabeling protocol using saline instead of radioactive indium-111 (sham radiolabeling [sham-RL]). Alternatively, a newly developed biotinylation protocol, a washing protocol, or an unmanipulated control sample were used. Platelet function was assessed by flow cytometry after stimulation with platelet agonists and labeling of platelets with platelet activation markers. To test whether platelets can be activated after transfusion, labeled platelets were transfused into nonobese diabetic/severe combined immunodeficiency mice, and samples were obtained 1 h after transfusion. RESULTS: The activation profile of biotinylated platelets was comparable to sham-RL platelets before transfusion except for significantly less α-degranulation and more phosphatidyl serine exposure on storage day 1/2. There was no significant difference between sham-RL and biotinylated platelets on storage day 6. Sham-RL and biotinylated platelets were significantly less activatable than washed and unmanipulated control platelets. After transfusion, the activation profile of biotinylated platelets was largely indistinguishable from unmanipulated ones. DISCUSSION: The decrease in activation level in biotinylated platelets we and others observed appears mainly due to the physical manipulation during the labeling process. In conclusion, biotinylated platelets allow for post-transfusion function assessment, a major advantage over radiolabeling.

Use of half red blood cell units in oncology patients during severe shortages to extend hospital supply.

BACKGROUND: The COVID-19 pandemic exerted an unprecedented impact on the blood supply from 2020 through 2022. As a result, throughout 2021 there were months our hospital had less than one-day supply of type O RBCs. To meet transfusion needs, whole RBC units were split into half units and issued to stable, non-bleeding patients. This single-institution, retrospective study examines time intervals to subsequent transfusion and total numbers of RBC units subsequently transfused after the first half or whole RBC unit. STUDY DESIGN AND METHODS: Patients who were transfused RBC between May 21, 2021 and November 1, 2021 were divided into in- and outpatient groups, then based on whether they received at least 1 half RBC unit or only whole RBC units during the study period. The time interval between this first half unit transfusion, or first whole unit transfusion in those who did not receive half units, and the subsequent RBC transfusion within 90 days was calculated and compared, as well as the total number of RBC units transfused 30 days after the first unit. RESULTS: In general, patients transfused with half units received a subsequent transfusion significantly earlier than those transfused with whole units. Additionally, receiving an index half unit was associated with more RBC transfusions in the following 30 days (p = .001). CONCLUSION: Transfusion of half RBC units during a severe RBC blood shortage can temporarily decrease RBC usage but will result in a shorter interval to the next transfusion and greater total number of RBC units transfused in subsequent days.

Molecular communication between red blood cells of different phenotypes during blood storage in mice.

BACKGROUND: The cellular and molecular changes during red blood cell (RBC) storage that affect posttransfusion recovery (PTR) remain incompletely understood. We have previously reported that RBCs of different storage biology cross-regulate each other when stored together (co-storage cross-regulation [CSCR]). However, the mechanism of CSCR is unclear. In the current study, we tested the hypothesis that CSCR involves acquisition of molecular signatures associated with PTR. STUDY DESIGN AND METHODS: The whole blood compartment of either B6 or FVB mice was biotinylated in vivo prior to blood collection and storage. Bio-B6 or Bio.FVB were stored with RBCs from B6 mice transgenic for green florescent protein (GFP) (B6.GFP). After storage, avidin-magnetic beads were used to simultaneous purify Bio-RBCs (positive selection) and B6.GFPs (negative selection). Isolated populations were analyzed by transfusion to establish PTR, and subjected to metabolomic and proteomic analysis. RESULTS: B6 RBCs acquired molecular signatures associated with stored FVB RBCs at both the metabolomic and proteomic level including metabolites associated with energy metabolism, oxidative stress regulation, and oxidative damage. Mitochondrial signatures were also acquired by B6 RBCs. Protein signatures acquired by B6 RBCs include proteins associated with vesiculation. CONCLUSION: The data presented herein demonstrate the appearance of multiple molecular changes from poor-storing RBCs in good-storing RBCs during co-storage. Whether this is a result of damage causing intrinsic molecular changes in B6 RBCs or if molecules of FVB RBC origin are transferred to B6 RBCs remains unclear. These studies broaden our mechanistic understanding of RBC storage (in particular) and potentially RBC biology (in general).

Patient and caregiver perceptions of the possibility of home blood transfusions.

BACKGROUND: Patients with hematologic malignancies (HM) often develop transfusion dependence. The patient and caregiver burdens associated with the need for frequent transfusions are high. Home blood transfusions has the potential to reduce these burdens, but is not widely practiced in the United States. We designed a qualitative study to evaluate the patient and caregiver perceptions of the potential for a home blood transfusion program. STUDY DESIGN AND METHODS: Eligible patients included Adult (≥18 years) patients who were English speaking and met the definition for transfusion dependence within 3 months of study enrollment. We identified and interviewed eligible participants (patients and caregivers), using a semi-structured interview guide to elicit patient perceptions of the acceptability, barriers, and benefits related to home blood product transfusions. Interviews were audio recorded and transcribed. Results were imported into NVivo 12 (version 12; QSR International, Burlington, VT) for coding and analysis. RESULTS: We recruited participants until we reached thematic saturation, which occurred at 29 participants (20 patients, 9 caregivers). Among the 20 patient participants, nine had MDS (45%) and 11 had acute leukemia (55%). Most of the patients (60%) reported getting one transfusion per week. Four themes emerged when the participants discussed their perception regarding the potential of a home blood transfusion program: (1) current in-person experience, (2) caregiver burden, (3) perceptions of home blood transfusions, and (4) interest in participating in a home blood transfusion program. CONCLUSION: The concept of home blood transfusions was well received and further research to study its implementation is warranted.

Donors with repeated blood product discards for filtration problems, clots or hemolysis: Causes and follow-up.

INTRODUCTION: Sanquin donor medicine department is informed when donations or their components are rejected. This can occur isolated or frequently. It is undesirable because the donations cannot be used and there may be an underlying medical cause. Based on regional approaches, a uniform procedure was developed. METHODS: Information about whole blood, plasma- plateletpheresis donations from which one or more components were rejected for filtration time (>2 h), hemolysis or clots were extracted from blood bank information system. After rejection of two successive components or donations or total ≥3 the donor is contacted. Depending on the medical history and investigation by the family doctor, the donor carrier is re-evaluated. We looked for the causes of the discarded products and performed a survey among blood services regarding polices with discarded products. RESULTS: One or more components from 1742 of about 2.2 million successful donations (0.08%) were rejected. The highest percentage of rejection was seen in plateletpheresis (1.5%), all for clots. No underlying medical causes were found. 24 whole blood donors were found to have sickle cell trait (SCT) and were permanently deferred. The policies for follow-up after discarded products or acceptance of SCT donors vary between the 16 blood banks. Six organizations do not follow-up donors and seven accept SCT for blood or plasma donation. CONCLUSION: Informing donors with repeated discarded products avoids the non-use of donations. Causes of repeated discarded products can be found by follow-up of donors. The results of the survey indicate a large discrepancy in policies applied worldwide.

Isohemagglutinin titration in pooled and apheresis platelets.

BACKGROUND: Platelet inventory constraints necessitate ABO-incompatible platelet transfusion. Many minimize the hemolytic impact by confirming low titre (LT) donor isohemagglutinins. This process is costly. Pathogen-reduced platelets (PRP) in platelet additive solutions (PAS) will dilute plasma and decrease high-titre isohemagglutinins (HT). We determined the proportion of HT platelets and incompatible transfusions for units suspended in plasma to reassess the need for titres following introduction of PRP/PAS. STUDY DESIGN AND METHODS: Our titre method is manual tube (1:50) dilution of platelet supernatant from apheresis or whole blood derived buffy coat pools suspended in plasma, tested with A1/B red cells. Testing included 49,058 pooled and 11,738 apheresis platelets over 4 years. The HT proportion, rate of out-of-group transfusions, and hemolytic reactions were determined. The impact of PAS dilution was estimated. RESULTS: Totally 60,796 platelet units were tested. Group O pooled and group B apheresis platelets had HT in 6.6% and 5.7%, respectively. Group A pooled and apheresis platelets included 2% with HT. Approximately 25% of platelets transfused were ABO-incompatible and no hemolytic reactions were reported. Based on the proportions of PAS-E and plasma for PRP platelets, plasma from each donor comprises 11 mL (6% of total volume) vs 20-257 mL in untreated pools. PAS-E will replace and dilute residual plasma by at least 50%. DISCUSSION: Rare platelet pools may demonstrate HT. PRP platelets with PAS will reduce titres and may abrogate the need for titration. A strategy of group specific transfusion or transfusion of group A PRP platelet transfusions may be a safe alternative.

Increased frequency of false-positive bacterial detection after implementation of new guidelines for large-volume delayed sampling of platelets.

BACKGROUND: The updated guidance for improving bacterial detection (BD) of platelets has included the implementation of large-volume delayed sampling (LVDS) with the addition of anaerobic culture bottles (BPNs) and sampling of each platelet split product. METHODS: The frequency of BD was reviewed during this LVDS time period in comparison with pre-LVDS and the Post-Approval Surveillance Study of Platelet Outcomes, Release Tested (PASSPORT) study (when BPNs were last used). RESULTS: There was more than a twofold increase in bottles inoculated per collection during LVDS, with an almost fivefold increase in sample volume collected. During LVDS, the concordance of split products within an initial reactive collection was only 8.7%. There was no difference in LVDS aerobic culture bottle (BPA) true positives (TPs), but there was a significant increase in LVDS false positives (FPs), p < .0001, compared to both PASSPORT and pre-LVDS, respectively. There was an increase in BPN TPs during LVDS (p < .05 compared to PASSPORT), with predominance of Cutibacter acnes (C. acnes), noted exclusively in BPN, and accounting for more than two-fifths of all organisms detected. Time to alarm during LVDS for TPs had two peaks with one due to C. acnes at 96 h compared to 17 h for non-C. acnes. DISCUSSION: The high FP frequency, along with low clinical significance of TPs found in BPNs, has led to the needless discard of inventory, as the utility of BPNs in BD for platelets is yet to be established and may require much larger studies.

Overestimation of fibrinogen concentration in cryoprecipitate by repeated freeze-thawing with long thawing period as used in the Clauss method.

BACKGROUND: Cryoprecipitate (CRY) is widely used for treating acquired hypofibrinogenemia. During our study to determine an optimal preparation method, we noticed that the measurement of fibrinogen concentration in CRY had a risk of overestimation. We analyzed this condition and mechanism. STUDY DESIGN AND METHODS: CRY was prepared from fresh frozen plasma (FFP) under four conditions: A, 30 h thawing time, 2 cycles; B, 24 h thawing time, 2 cycles; C, 30 h thawing time, 1 cycle; and D, 24 h thawing time, 1 cycle. Then, fibrinogen concentrations in CRY and cryosupernatant (CS) were measured by the Clauss method. RESULTS: Purification (CRY/CRY+CS) and recovery (CRY/FFP) rates in CRY prepared under 2-cycle conditions were higher than those under 1 cycle. However, recovery rates often exceeded 100%, particularly in the case of CRY prepared under A condition, and fibrinogen concentrations calculated by direct measurement were higher than those indirectly calculated from FFP and CS, suggesting an overestimation of fibrinogen values. The level of soluble fibrin monomer complex was considerably higher in CRY prepared under A than under D condition, indicating that CRY adopted a hypercoagulated state. We further found that repeated thawing/freezing increased fibrinogen values as measured by the Clauss method while mechanical vortexing did not. DISCUSSION: Our findings suggest that direct assessment of fibrinogen contents in CRY prepared by repeated freeze-thawing with a longer thawing period presents a higher risk of overestimation. For the purpose of quality control, we propose an alternative method to indirectly estimate fibrinogen concentrations in CRY from those of CS and FFP.

Three patients highlighting potential pitfalls in platelet refractory testing.

BACKGROUND: Platelet-transfusion refractory (PR) patients do not achieve expected post-transfusion platelet counts. We investigate suspected PR patients with post-transfusion platelet counts, indirect platelet antibody screens (ind-PAS), Class I HLA antibody tests (HLA-Scr), and physical platelet crossmatch (PXM) studies. STUDY DESIGN AND METHODS: The three following cases describe possible pitfalls of laboratory tests used in PR workup and management. RESULTS: Case #1: Antibody testing detected antibodies to only HLA-B13, corresponding to a 4% calculated panel reactive antibodies (CPRA; 96% predicted donor compatibility). However, PXM showed the patient compatible with 11/14 (79%) donors; two of the PXM-incompatible units were ABO-incompatible. Case #2: PXM revealed compatibility with 1/14 screened donors; however, the patient did not respond to the product from the compatible donor. The patient did respond to HLA-matched product. Dilution studies provided evidence of the prozone effect, which caused negative PXM despite clinically relevant antibodies. Case #3: There was a discrepancy between the ind-PAS and HLA-Scr. Ind-PAS was negative for HLA antibodies, while HLA-Scr was positive and specificity testing corresponded to 38% CPRA. Per the package insert, the sensitivity of ind-PAS is ~85% compared to HLA-Scr. DISCUSSION: These cases highlight the importance of investigating incongruent results. Cases #1 and #2 demonstrate PXM pitfalls: ABO incompatibility can result in positive PXM and false-negative PXM can occur in the setting of the prozone effect. Case #3 reveals the importance of knowing a test's sensitivity. Centers that only perform ind-PAS may fail to detect HLA antibodies.

The oxygen saturation of red blood cell concentrates: The basis for a novel index of red cell oxidative stress.

BACKGROUND: Oxidative stress is a major driving force in the development of storage lesions in red cell concentrates (RCCs). Unlike manufactured pharmaceuticals, differences in component preparation methods and genetic/physiological status of donors result in nonuniform biochemical characteristics of RCCs. Various characteristics of donated blood on oxygen saturation (SO2 ) distribution were investigated, and a model to estimate potential oxidative stress burden of stored RCC at transfusion is proposed. STUDY DESIGN AND METHODS: The oxygen content of freshly prepared RCCs (770) was quantified noninvasively as fractional hemoglobin saturation (SO2 ) with visible reflectance spectrometry. Using separate RCCs and mimicking typical handling of RCCs during routine storage, evolution of SO2 was followed for construction of an empirical model. Based on this model, the oxygen exposure index (OEI) was formulated to estimate the accumulated oxygen exposure burden of RCC at the time of transfusion. RESULTS: The SO2 of RCCs varied widely at donation (mean 43% ± 1.3%; range 20%-93%). Multivariate regression model showed that sex and processing method had small effects on SO2 (R2  = 0.12), indicating that variability was mainly attributed to other individual donor characteristics. Storage simulation model indicated that median SO2 increased gradually over 6 weeks (approx. 1.3 fold), while OEI increased at a faster rate (approx. eight-fold). CONCLUSION: In addition to storage age, the OEI provides a potential new metric to assess the quality of RCCs at the time of transfusion in terms of their oxidative stress. In future studies, a single noninvasive measurement during storage could link OEI to clinical outcomes in transfusion recipients.

Donor variation in stored platelets: Higher metabolic rates of platelets are associated with mean platelet volume, activation and donor health.

BACKGROUND: Platelets (PLTs) differ in glycolytic activity, resulting in rapid acidification of 'poor' storing PLT concentrates (PCs) in plasma, or depletion of glucose when stored in PLT additive solution (PAS). We aimed to understand why PLT glycolysis rates vary between donors and how this affects storage performance. STUDY DESIGN AND METHODS: Buffy coats from donors <45, 45-70 and >70 years were selected and single-donor PCs in plasma or PAS-E were prepared. PCs were stored for 8 days at 22 ± 2°C and sampled regularly for analysis. Mitochondrial activity was analyzed with an Oroboros oxygraph. Age groups, or subgroups divided into quartiles based on glucose consumption, were analyzed with ANOVA. RESULTS: In each comparison, PCs of the different groups were not different in volume and cellular composition. PLTs with the highest glucose consumption had a higher initial mean platelet volume (MPV) and developed higher CD62P expression and Annexin A5 binding during storage. Higher glycolytic activity in these PLTs was not a compensation for lower mitochondrial ATP production, because mitochondrial ATP-linked respiration of fresh PLTs correlated positively with MPV (R2  = 0.71). Donors of high glucose-consuming PLTs had more health-related issues. Storage properties of PCs from donors over 70 were not significantly different compared to PCs from donors younger than 45 years. CONCLUSIONS: High glucose-consuming PCs developing higher activation levels, not only displayed enhanced mitochondrial activity but were also found to contain larger PLTs, as determined by MPV. Storage performance of PLTs was found to be associated with donor health, but not with donor age.

Validated transport conditions maintain the quality of washed red blood cells.

BACKGROUND: Washing red blood cell (RBC) units prior to transfusion is indicated for certain patients. In the United States, units stored at 1°C-6°C or transported at 1°C-10°C are available for issue up to 24 h, if not used immediately. The washing procedure commonly utilizes room temperature saline resulting in units starting out above the allowed temperature range. This leads to wastage if units are issued and returned too quickly before having a chance to equilibrate in a transport cooler. STUDY DESIGN AND METHODS: Here we performed an experimental study of washed RBC quality comparing "ideal" storage conditions in a blood bank refrigerator to a "real-world" simulation of unit transport, including holding in a transport cooler. Twelve RBC units were washed and allocated evenly into either condition. RESULTS: Measurements at 0, 1, 3, 6, 12, and 24 h post-washing revealed that placement in a transport cooler was associated with higher unit temperature prior to 12 h (p = .013) with a maximum difference of 9.3°C. Despite this difference, several measures of unit quality including extracellular potassium, pH, lactate, and free hemoglobin were indistinguishable between conditions (p = .382, .224, .286, .691, respectively). We selected half of the tested units from our irradiated inventory and confirmed increased potassium leak (p < .001) and accumulation of free hemoglobin (p = .012) in irradiated units. DISCUSSION: Washed units stored under approved transport conditions are acceptable to return to inventory up to 24 h after washing and we provide a prediction interval-based temperature threshold for rejecting these units, permitting reduced waste.

Safety and tolerability of solvent/detergent-treated plasma for pediatric patients requiring therapeutic plasma exchange: An open-label, multicenter, postmarketing study.

BACKGROUND: This study investigated the real-world safety and tolerability of solvent/detergent-treated (S/D) plasma for pediatric patients requiring therapeutic plasma exchange (TPE). STUDY DESIGN AND METHODS: LAS-213 was a multicenter, open-label, interventional, phase 4 study. Patients (≥2 to ≤20 years) receiving TPE therapy were eligible. A total plasma volume of 40-60 ml/kg was recommended, with an infusion rate not exceeding 0.020-0.025 citrate/kg body weight/min (<1 ml/kg body weight/min). The primary endpoint was assessment of safety, monitoring the following: serious adverse events (SAEs), adverse drug reactions (ADRs), thrombotic events (TEs), thromboembolic events (TEEs), and specific laboratory tests. RESULTS: In total, 41 children (2 to <12 years [n = 15]; 12 to <17 years [n = 13]; ≥17 years [n = 13]) underwent 102 TPEs with a total of 135,137 ml of S/D plasma exchanged. Each patient group received between 1 and 6 TPEs (mean: 2.5 TPEs). Actual dose administered per TPE was 4-72 ml/kg (mean: 28.6 ml/kg), with a mean total volume of 1324.9 ml (range: 113-4000 ml). Overall safety was excellent for 96/102 (94.0%) TPEs. Six TPEs had a "moderate" safety profile for four patients experiencing eight ADRs. Of these, seven were mild in intensity and one (pyrexia) was moderate, all resolving by study end. Mild citrate toxicity (n = 2) was the most common ADR. One SAE was reported but was unrelated to the study drug. No TEs, TEEs, or changes in laboratory safety parameters were reported. CONCLUSION: S/D plasma was well tolerated and demonstrated favorable safety, supporting the use of S/D plasma for TPE in pediatrics.

Cryoprecipitated anti-hemophiliac factor manufactured from plasma frozen within 24 h after phlebotomy meets AABB quality standards.

BACKGROUND: Cryoprecipitated antihemophiliac factor (CryoAHF) manufacturing in the US has not kept pace with the increasing demand for hospital transfusion services. Association for Advancement of Blood and Biologics (AABB) and Food and Drug Administration (FDA) require that CryoAHF be manufactured from fresh frozen plasma within 8 h (FFP). We evaluated whether CryoAHF manufactured from plasma frozen within 24 h (PF24) met regulatory quality control (QC) requirements to increase available plasma for CryoAHF. STUDY DESIGN AND METHODS: In a "worst-case scenario" feasibility study, we produced 21 single units of CryoAHF from type-O whole blood-derived PF24 frozen between 20 and 24 h after collection. A follow-up QC validation was conducted wherein 69 PF24 units across three sites were manufactured into CryoAHF. Factor VIII (FVIII) and fibrinogen levels were measured. RESULTS: CryoAHF manufactured in our feasibility study from PF24 contained FVIII levels of 208 ± 61 IU (mean ± SD) and 509 ± 152 mg of fibrinogen levels per unit. CryoAHF manufactured in our QC validation from PF24 yielded FVIII levels of 214 ± 58 IU and 607 ± 176 mg of fibrinogen levels per unit. The coagulation factor levels from each of the individual CryoAHF units exceeded the minimum AABB and FDA requirement of ≥80 IU of FVIII per unit and ≥150 mg of fibrinogen per unit. There was no decrease in FVIII or fibrinogen levels in CryoAHF produced from PF24 as compared to historic QC results of CryoAHF produced from FFP. CONCLUSION: These studies demonstrated that CryoAHF produced from PF24 meets AABB and FDA QC requirements. FDA approved the American Red Cross request to manufacture CryoAHF singles and pools from PF24 as source material.

Efficacy and safety of fibrinogen concentrate for perioperative prophylaxis of bleeding in adult, adolescent, and pediatric patients with congenital fibrinogen deficiency: FORMA-02 and FORMA-04 clinical trials.

BACKGROUND: Congenital fibrinogen deficiency (CFD) is a rare coagulation disorder placing patients at increased bleeding risk. Human fibrinogen concentrate (HFC) represents current standard of care for fibrinogen replacement in CFD, however, limited data are available on HFC for prophylactic administration before/during surgery. Here, we report results and dosing considerations for HFC treatment in perioperative bleeding management in adult, adolescent, and pediatric patients with CFD. STUDY DESIGN AND METHODS: FORMA-02/FORMA-04 were multinational, prospective, open-label, uncontrolled Phase 3 HFC efficacy/safety studies for surgical bleeding prophylaxis in adult/adolescent (≥12 years) and pediatric patients (<12 years) respectively. HFC dosing was calculated to achieve pre-established target fibrinogen plasma levels. Overall hemostatic efficacy was assessed as success/failure by an Independent Data Monitoring and Endpoint Adjudication Committee (IDMEAC) according to objective criteria. RESULTS: Twelve patients (≥12 years, N = 9; <12 years, N = 3) received HFC for surgical prophylaxis (15 surgeries; 13 minor, 2 major). Eleven minor surgeries in patients aged ≥12 years required a median of 1 infusion (range; 1-5), with a mean (±SD) dose of 93.50 mg/kg [±41.43] and two minor surgeries in patients <12 years required 1 infusion (91.55 mg/kg [±23.40]). The major surgery in an adult patient required eight infusions (225.3 mg/kg total dose). The major surgery in a pediatric patient required six infusions (450.4 mg/kg). All surgeries were rated successful by the IDMEAC. DISCUSSION: In adults/adolescents and pediatric patients with fibrinogen deficiency, HFC treatment for hemostatic management during/after minor and major surgery was successful, with efficacy comparable across the different age groups.

Spray-dried plasma: A post-traumatic blood "bridge" for life-saving resuscitation.

Massive bleeding remains a major source of morbidity and mortality worldwide. Recent studies have shed light on the pathophysiology of traumatic-induced coagulopathy and the central role of endotheliopathy. Transfusion therapy has changed dramatically in the last decade with use of red cells and plasma in a 1:1 ratio. The use of early transfusion increases the likelihood of a favorable outcome. Early intervention-preferably less than 60 min of injury-is a major factor in improved survival. Experience with dried plasma products-lyophilized or freeze-dried-in Europe and South Africa has demonstrated both safety and efficacy. Dry plasma products are not available in the United States but several products are in development. Spray-dried plasma contains clinically meaningful levels of coagulation activity and in vitro data suggest robust ability to generate thrombus. The decentralized, blood-center based manufacturing model of spray-dried plasma offers advantages for availability to meet routine and extraordinary demands.

Supplemental findings of the 2019 National Blood Collection and Utilization Survey.

INTRODUCTION: Supplemental data from the 2019 National Blood Collection and Utilization Survey (NBCUS) are presented and include findings on donor characteristics, autologous and directed donations and transfusions, platelets (PLTs), plasma and granulocyte transfusions, pediatric transfusions, transfusion-associated adverse events, cost of blood units, hospital policies and practices, and implementation of blood safety measures, including pathogen reduction technology (PRT). METHODS: National estimates were produced using weighting and imputation methods for a number of donors, donations, donor deferrals, autologous and directed donations and transfusions, PLT and plasma collections and transfusions, a number of crossmatch procedures, a number of units irradiated and leukoreduced, pediatric transfusions, and transfusion-associated adverse events. RESULTS: Between 2017 and 2019, there was a slight decrease in successful donations by 1.1%. Donations by persons aged 16-18 decreased by 10.1% while donations among donors >65 years increased by 10.5%. From 2017 to 2019, the median price paid for blood components by hospitals for leukoreduced red blood cell units, leukoreduced apheresis PLT units, and for fresh frozen plasma units continued to decrease. The rate of life-threatening transfusion-related adverse reactions continued to decrease. Most whole blood/red blood cell units (97%) and PLT units (97%) were leukoreduced. CONCLUSION: Blood donations decreased between 2017 and 2019. Donations from younger donors continued to decline while donations among older donors have steadily increased. Prices paid for blood products by hospitals decreased. Implementation of PRT among blood centers and hospitals is slowly expanding.

Osmotic hemolysis is a donor-specific feature of red blood cells under various storage conditions and genetic backgrounds.

BACKGROUND: Transfusion research has recently focused on the discovery of red blood cell (RBC) storage capacity biomarkers and the elucidation of donor variation effects. This shift of focus can further strengthen personalization of transfusion therapy, by revealing probable links between donor biology, RBC storage lesion profile, and posttransfusion performance. STUDY DESIGN AND METHODS: We performed a paired correlation analysis of osmotic fragility in freshly drawn RBCs and during cold storage in different preservative solutions at weekly intervals until unit's expiration date (n = 231), or following 24 h reconstitution in allogeneic plasma (n = 32) from healthy controls or transfusion-dependent beta-thalassemia patients. RESULTS: We observed exceptional correlation profiles (r > 0.700, p < 10-5 in most cases) of RBC osmotic fragility in the ensemble of samples, as well as in subgroups characterized by distinct genetic backgrounds (sex, beta-thalassemia traits, glucose-6-phosphate dehydrogenase deficiency) and storage strategies (additive solutions, whole blood, RBC concentrates). The mean corpuscular fragility (MCF) of fresh and stored RBCs at each storage time significantly correlated with the MCF of stored RBCs measured at all subsequent time points of the storage period (e.g., MCF values of storage day 21 correlated with those of storage days 28, 35 and 42). A similar correlation profile was also observed between the osmotic hemolysis of fresh/stored RBCs before and following in vitro reconstitution in plasma from healthy controls or beta-thalassemia patients. CONCLUSION: Our findings highlighted the potential of osmotic fragility to serve as a donor-signature on RBCs at every step of any individual transfusion chain (donor, blood product, and probably, recipient).

Effects of hypoxic storage on the efficacy of gamma irradiation in abrogating lymphocyte proliferation and on the quality of gamma-irradiated red blood cells in additive solution 3.

BACKGROUND: Gamma irradiation of blood products is used to prevent transfusion-associated graft-versus-host disease by inhibiting the proliferation of lymphocytes that are implicated in the disease. Gamma irradiation also damages the red blood cells (RBCs). It is unknown whether hypoxia reduces the efficacy of gamma irradiation in inhibiting lymphocyte proliferation (LP). The objectives of the study were to investigate the effects of hypoxia on gamma irradiation-induced inhibition of LP and on the in vitro properties of RBCs. MATERIALS AND METHODS: Forty-four units (300-340 ml each) of less than 8-h-old ABO-matched leukocyte reduced red cell concentrates (LR-RCC) in additive solution 3 were pooled in pairs. Peripheral blood mononuclear cells were isolated from non-leukocyte reduced RCCs and added back to the pool at a final concentration of 2 × 105 /ml. The pool was divided equally into a conventional storage bag A and a hypoxic processing and storage bag B. The units were gamma-irradiated at 25Gy on day 7 for the LP experiment and on either day 7 or 14 for the RBC quality experiments. LP was measured using a limiting dilution assay, and several in vitro metrics of RBCs were measured. RESULTS: Gamma irradiation inhibited T-lymphocyte proliferation by 4.7 × 104 -fold reduction in both hypoxic and conventional storage. The in vitro metrics of RBC quality were better preserved in hypoxic storage. DISCUSSION: T lymphocytes present in hypoxic RBC are equally susceptible to gamma irradiation as conventional storage. Hypoxic storage also reduces the deleterious effects of gamma irradiation on RBCs.