Introduction of EUBIS standards to upgrade inspections of blood establishments to improve the safety of blood transfusion: The Polish experience.

BACKGROUND AND OBJECTIVES: The competent authority (CA) responsible for external inspections of Polish blood establishments (BEs) and supervision of the quality system is the Institute of Haematology and Transfusion Medicine (IHTM). Before the implementation of the European Blood Inspection System (EuBIS) classification of non-compliance, the IHTM inspections were conducted according to national guidelines and the non-compliance-related recommendations were based on the inspectors' own experience and interpretation of the observed problems. Since 2009, IHTM inspections were already performed according to EuBIS guidelines. The study assessed the impact of the EuBIS classification on the IHTM recommendations. We assumed that the implementation of consistent assessment criteria contributed to the upgrading of the quality of BE inspections. MATERIALS AND METHODS: BE-inspection protocols; 30 from 2009 to 2010 and 61 from 2016 to 2019. Non-compliance-related recommendations were classified according to the seriousness of non-compliances (critical, major, other significant, and observation) and also to the area of BE activity (documentation, organisation of work, qualification and validation, pathway from donor qualification to blood component-issue, quality control of blood components, adverse events and reactions). RESULTS: The recommendations mostly referred to document-keeping and work organisation and were distributed as follows: 2009-2 critical (others unclassified), 2010-1-13 major, 4-25 other significant and 1-7 suggestions, 2016-2019-3-9 critical, 90-196 major, and 157-297 other significant as well as 14-22 suggestions. CONCLUSION: Polish BEs still require: integrated document management, analysis of IHTM recommendations, implementation of corrective and preventive measures and personnel training in identifying similar non-compliances in other procedures.

Feasibility, safety, and tolerability of two modalities of plasma exchange with albumin replacement to treat elderly patients with Alzheimer's disease in the AMBAR study.

BACKGROUND: In the Alzheimer Management by Albumin Replacement (AMBAR) study, mild-to-moderate Alzheimer's disease (AD) patients were treated with a plasma exchange (PE) program. Feasibility and safety of PE in this specific population are poorly understood and were analyzed in detail in this study. METHODS: Qualified patients were treated with 6 weeks of weekly conventional therapeutic plasma exchange (TPE) with albumin replacement followed by monthly low-volume plasma exchange (LVPE) for 12 months. The patients were divided into four groups: placebo (sham PE treatment), low-albumin (20 g), low-albumin + intravenous immunoglobulin (IVIG) (10 g), and high-albumin (40 g) + IVIG (20 g). Adverse events (AEs) were recorded and analyzed for all PE treatment groups and PE modalities. RESULTS: PE procedure-related AEs were more common in the active treatment groups (16.9% out of 1283 TPE and 12.5% out of 2203 LVPE were associated with at least one AE, a similar rate than in other PE indications) than in the placebo group (0.7% out of 1223 sham PE). Percentage of procedures with at least one AEs was higher with central venous access compared to peripheral venous access in all three active treatment groups (20.1% vs 13.1%, respectively). CONCLUSION: The TPE and LVPE procedures used in the AMBAR study on mild-to-moderate AD population were as safe and feasible as in other therapeutic applications of PE or routine plasmapheresis.

Standardization of cellular therapy terminology, coding and labeling: a review.

The 1990s saw rapid growth in international activity in hematopoietic cell transplantation. As national donor registries were established and international collaboration increased, a need to transfer cellular therapy products across national borders emerged. A lack of international standards for identification, terminology and labeling resulted in significant challenges for import and export. Twenty years of effort by a large group of experts supported by professional societies and accreditation bodies has today achieved a high degree of standardization. This review highlights the main landmarks in this journey and serves as a reminder of the importance of taking the "long view" when working toward international standardization. It demonstrates the need for continual maintenance and enhancement of standards to meet the changing needs of the cell therapy industry and highlights recent developments in ISBT 128.

Passive order auditing associated with reductions in red blood cell utilization: National blood shortage experience.

BACKGROUND: Decreased blood collection during the Coronavirus Disease 2019 (COVID-19) pandemic resulted in long-term red blood cell (RBC) shortages in the United States. In an effort to conserve RBCs, the existing passive alert system for auditing inpatient transfusions was modified to activate at a lower hemoglobin threshold (6.5 g/dL instead of 7.0 g/dL for stable, nonbleeding inpatients) during a 9-month shortage at an academic medical center. Hemoglobin levels prior to RBC transfusions were compared for inpatients receiving RBC transfusions to determine whether RBC utilization changed during the intervention. STUDY DESIGN AND METHODS: This retrospective study compared the number of single-unit RBC transfusions and hemoglobin levels prior to RBC transfusion among inpatients during the 9 months of the intervention (Period 2, 06/01/2021-2/28/2022) to the same period of the previous year (Period 1, 06/01/2020-2/28/2021). RESULTS: Overall full unit RBC transfusions to inpatients decreased by 15% from 5182 to 4421. Of all transfusions, 50.3% and 49.8% were single-unit RBC transfusions in Period 1 and Period 2, respectively. The incidence rate difference and incidence rate ratio of single RBC units transfused per 1000 patient days were significantly decreased (p = 0.0007). The average pre-transfusion hemoglobin level significantly decreased from 7.18 g/dL to 7.05 g/dL (p = 0.0002), largely due to significant decreases in hemoglobin transfusion triggers for adult inpatient ward transfusions. DISCUSSION: Modification of the passive alert system was associated with significantly decreased RBC utilization during a long-term RBC shortage. Modification of transfusion criteria recommended by passive alerts may be a feasible option to decrease RBC utilization at centers during long-term RBC shortages.

Evaluation of amotosalen and UVA pathogen-reduced apheresis platelets after 7-day storage.

BACKGROUND: Amotosalen/UVA pathogen-reduced platelet components (PRPCs) with storage up to 7 days are standard of care in France, Switzerland, and Austria. PRPCs provide effective hemostasis with reduced risk of transfusion-transmitted infections and transfusion-associated graft versus host disease, reduced wastage and improved availability compared with 5-day-stored PCs. This study evaluated the potency of 7-day PRPCs by in vitro characterization and in vivo pharmacokinetic analysis of autologous PCs. STUDY DESIGN AND METHODS: The in vitro characteristics of 7-day-stored apheresis PRPCs suspended in 100% plasma or 65% platelet additive solution (PAS-3)/35% plasma, thrombin generation, and in vivo radiolabeled post-transfusion recovery and survival of 7-day-stored PRPCs suspended in 100% plasma were compared with either 7-day-stored or fresh autologous conventional platelets. RESULTS: PRPCs after 7 days of storage maintained pH, platelet dose, in vitro physiologic characteristics, and thrombin generation when compared to conventional 7-day PCs. In vivo, the mean post-transfusion survival was 151.4 ± 20.1 h for 7-day PRPCs in 100% plasma (Test) versus 209.6 ± 13.9 h for the fresh autologous platelets (Control), (T-ΔC: 72.3 ± 8.8%: 95% confidence interval [CI]: 68.5, 76.1) and mean 24-h post-transfusion recovery 37.6 ± 8.4% for Test versus 56.8 ± 9.2% for Control (T-ΔC: 66.2 ± 11.2%; 95% CI: 61.3, 71.1). DISCUSSION: PRPCs collected in both 100% plasma as well as 65% PAS-3/35% plasma and stored for 7 days retained in vitro physiologic characteristics. PRPCs stored in 100% plasma for 7 days retained in vivo survival. Lower in vivo post-radiolabeled autologous platelet recovery is consistent with reported reduced count increments for allogenic transfusion.

Neuropsychological, neuropsychiatric, and quality-of-life assessments in Alzheimer's disease patients treated with plasma exchange with albumin replacement from the randomized AMBAR study.

INTRODUCTION: We report the effects of plasma exchange (PE) with albumin replacement on neuropsychological, neuropsychiatric, and quality-of-life (QoL) outcomes in mild-to-moderate Alzheimer's disease (AD) patients in a phase 2b/3 trial (Alzheimer's Management by Albumin Replacement [AMBAR] study). METHODS: Three hundred forty-seven patients were randomized into placebo (sham-PE) and three PE-treatment arms with low/high doses of albumin, with/without intravenous immunoglobulin (IVIG). Specific test measurements were performed at baseline; month 2 (weekly conventional PE); months 6, 9, and 12 (monthly low-volume PE [LVPE]); and month 14. RESULTS: The PE-treated mild-AD cohort improved their language fluency and processing speed versus placebo at month 14 (effect sizes: >100%; P-values: .03 to .001). The moderate-AD cohort significantly improved short-term verbal memory (effect sizes: 94% to >100%; P-values: .02 to .003). The progression of the neuropsychiatric symptoms of PE-treated was similar to placebo. Mild-AD patients showed improved QoL (P-values: .04 to .008). DISCUSSION: PE-treated AD patients showed improvement in memory, language abilities, processing speed, and QoL-AD. No worsening of their psychoaffective status was observed.

Consensus International Council for Commonality in Blood Banking Automation-International Society for Cell & Gene Therapy statement on standard nomenclature abbreviations for the tissue of origin of mesenchymal stromal cells.

The Cellular Therapy Coding and Labeling Advisory Group of the International Council for Commonality in Blood Banking Automation and the International Society for Cell & Gene Therapy mesenchymal stromal cell (MSC) committee are providing specific recommendations on abbreviating tissue sources of culture-adapted MSCs. These recommendations include using abbreviations based on the ISBT 128 terminology model that specifies standard class names to distinguish cell types and tissue sources for culture-adapted MSCs. Thus, MSCs from bone marrow are MSC(M), MSCs from cord blood are MSC(CB), MSCs from adipose tissue are MSC(AT) and MSCs from Wharton's jelly are MSC(WJ). Additional recommendations include using these abbreviations through the full spectrum of pre-clinical, translational and clinical research for the development of culture-adapted MSC products. This does not apply to basic research focused on investigating the developmental origins, identity or functionalities of endogenous progenitor cells in different tissues. These recommendations will serve to harmonize nomenclature in describing research and development surrounding culture-adapted MSCs, many of which are destined for clinical and/or commercial translation. These recommendations will also serve to align research and development efforts on culture-adapted MSCs with other cell therapy products.

Variations in novel cellular therapy products manufacturing.

BACKGROUND AIMS: At the frontier of transfusion medicine and transplantation, the field of cellular therapy is emerging. Most novel cellular therapy products are produced under investigational protocols with no clear standardization across cell processing centers. Thus, the purpose of this study was to uncover any variations in manufacturing practices for similar cellular therapy products across different cell processing laboratories worldwide. METHODS: An exploratory survey that was designed to identify variations in manufacturing practices in novel cellular therapy products was sent to cell processing laboratory directors worldwide. The questionnaire focused on the manufacturing life cycle of different cell therapies (i.e., collection, purification, in vitro expansion, freezing and storage, and thawing and washing), as well as the level of regulations followed to process each product type. RESULTS: The majority of the centers processed hematopoietic progenitor cells (HPCs) from peripheral blood (n = 18), bone marrow (n = 16) or cord blood (n = 19), making HPCs the most commonly processed cells. The next most commonly produced cellular therapies were lymphocytes (n = 19) followed by mesenchymal stromal cells (n = 14), dendritic cells (n = 9) and natural killer (NK) cells (n = 9). A minority of centers (<5) processed pancreatic islet cells (n = 4), neural cells (n = 3) and induced-pluripotent stem cells (n = 3). Thirty-two laboratories processed products under an investigational status, for either phase I/II (n = 27) or phase III (n = 17) clinical trials. If purification methods were used, these varied for the type of product processed and by institution. Environmental monitoring methods also varied by product type and institution. CONCLUSION: This exploratory survey shows a wide variation in cellular therapy manufacturing practices across different cell processing laboratories. A better understanding of the effect of these variations on the quality of these cell-based therapies will be important to assess for further process evaluation and development.

A multicenter evaluation of heterogeneity in cellular therapy processing laboratory procedure times to assess workload capacity.

BACKGROUND: Growth in size and complexity of clinical hematopoietic progenitor cell (HPC) transplant programs necessitates parallel increases in cellular therapy laboratory (CTL) workload. Typically individually developed, HPC product processing is labor and time intensive. Variation in procedure type and numbers across CTLs complicates direct comparisons, and benchmark data are not readily available. STUDY DESIGN AND METHODS: Studies were undertaken at seven CTLs. Transplant volume and staff numbers were determined. Staff recorded time performing tasks broken down into steps: paperwork, product acceptance, transport/infusion, processing, and cryopreservation. Times were added to obtain total times for 15 common CTL procedures. RESULTS: Annual transplant volume ranged from 53.4 to 463.2, with products processed by a range of 2 to 10 dedicated CTL staff. Paperwork time constituted 23.7% to 62.3% total time; product processing time accounted for 1.8 (for National Marrow Donor Program product receipt) to 62.6% (for red blood cell reduction of allogeneic HPC products from bone marrow) of total processing time. Mean time for 15 procedures ranged from 1.27 to 8.28 hours (standard deviation range, 0.35-2.71 hr). Mean time for products from bone marrow versus peripheral blood was 6.6 ± 2.0 versus 5.5 ± 1.1 hours (p = 0.02). Cryopreservation (6.5 ± 1.6 vs. 4.4 ± 0.85 hr; p < 0.01) and manipulation (6.4 ± 1.5 vs. 4.4 ± 0.85 hr; p < 0.01) added time. CONCLUSION: CTL procedures are time intensive, with wide intra- and inter-CTL variation. Paperwork accounted for substantial portion of total time across procedures. Bone marrow source, cryopreservation, and manipulation contributed to longer times. These findings provide concrete data on which to build regarding CTL workload capacity.

A randomized, controlled clinical trial of plasma exchange with albumin replacement for Alzheimer's disease: Primary results of the AMBAR Study.

INTRODUCTION: This phase 2b/3 trial examined the effects of plasma exchange (PE) in patients with mild-to-moderate Alzheimer's disease (AD). METHODS: Three hundred forty-seven patients (496 screened) were randomized (1:1:1:1) into three PE treatment arms with different doses of albumin and intravenous immunoglobulin replacement (6-week period of weekly conventional PE followed by a 12-month period of monthly low-volume PE), and placebo (sham). RESULTS: PE-treated patients performed significantly better than placebo for the co-primary endpoints: change from baseline of Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL; P = .03; 52% less decline) with a trend for Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog; P = .06; 66% less decline) scores at month 14. Moderate-AD patients (baseline Mini-Mental State Examination [MMSE] 18-21) scored better on ADCS-ADL (P = .002) and ADAS-Cog (P = .05), 61% less decline both. There were no changes in mild-AD patients (MMSE 22-26). PE-treated patients scored better on the Clinical Dementia Rating Sum of Boxes (CDR-sb) (P = .002; 71% less decline) and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) (P < .0001; 100% less decline) scales. DISCUSSION: This trial suggests that PE with albumin replacement could slow cognitive and functional decline in AD, although further studies are warranted.

Assessing the risk of Babesia to the United States blood supply using a risk-based decision-making approach: Report of AABB's Ad Hoc Babesia Policy Working Group (original report).

Recognizing the increasing threat of transfusion-transmitted babesiosis to the US blood supply, the AABB Board of Directors tasked an Ad Hoc Babesia Policy Working Group (the Working Group) to use the Alliance of Blood Operators' risk-based decision-making (RBDM) framework to assess the risks and benefits of introducing Babesia donation testing in the United States. The regional nature of the Babesia microti risk added complexity to the RBDM assessment because of the unique operational and financial considerations for operators and hospitals located in endemic states. Therefore, the assessment considered safety, product availability, sector sustainability, and technology availability. After assessing safety risk, economic and operational impact, reimbursement equity, ethical considerations, and stakeholder feedback from two consultations, the Working Group concluded that a regional approach to donor screening in endemic states was appropriate because it applied the intervention where the risk was highest and appropriately allocated cost to the risk. Nucleic acid testing using a ribosomal RNA template was the recommended intervention because it was the most cost-effective, resulted in no wasted units, and captured similar numbers of infections as antibody plus DNA-based polymerase chain reaction. The current model for blood reimbursement was maintained but AABB was encouraged to facilitate collection of data to identify threats to sector sustainability in endemic states. Babesia expansion was acknowledged with a mechanism to regularly reevaluate what are "endemic states." Finally, given that public awareness of the Babesia threat is the first line of defense, AABB should work with appropriate agencies for general education about the health risk from B. microti.

Routine use of Day 6 and Day 7 platelets with rapid testing: two hospitals assess impact 1 year after implementation.

BACKGROUND: In March 2016 the US Food and Drug Administration published a draft guidance to enhance the safety of platelets (PLTs) for transfusion. Options for hospital transfusion services include the use of rapid testing to extend apheresis PLT dating for up to 7 days. This report describes the impact of routine use of Day 6 and Day 7 PLTs at two hospital transfusion services 1 year after implementation of rapid testing for outdate extension. STUDY DESIGN AND METHODS: PLT transfusion and inventory data were obtained from two hospital-based transfusion services for 12 months before and 12 months after implementation of rapid testing to extend the outdate of apheresis PLTs to 7 days. RESULTS: The outdate rate decreased from 5% to 2% (p < 0.0001) at Hospital 1 and 28% to 14% (p < 0.001) at Hospital 2 after implementation of routine use of Day 6 and Day 7 PLTs. The proportion of apheresis PLT units that underwent secondary screening for bacterial contamination before transfusion in the postimplementation period increased from 33% to 54% at Hospital 1 and from 0% to 31% at Hospital 2. CONCLUSION: A significant decrease in outdate rate was observed after routine use of Day 6 and Day 7 PLTs. Use of rapid testing to extend PLT outdate also resulted in a larger proportion of PLTs that underwent secondary testing for bacterial contamination before transfusion. These observations demonstrate that use of rapid testing to extend apheresis PLT dating up to 7 days enhances the safety of PLTs for transfusion and decreases wastage of a limited resource.

Apheresis buffy coat collection without photoactivation has no effect on apoptosis, cell proliferation, and total viability of mononuclear cells collected using photopheresis systems.

BACKGROUND: Extracorporeal photopheresis (ECP) has been approved for the treatment of advanced cutaneous T-cell lymphoma since 1988. While the precise mechanisms resulting in clinical effects are not fully understood, the photoactivation of mononuclear cells (MNCs) using ultraviolet A (UVA) light and methoxsalen is believed to be the predominant initiating process. The effects of MNC passage through the instrument without photoactivation are unknown. The objective of this study was to evaluate the effect of cell processing through the photopheresis instruments on MNCs. STUDY DESIGN AND METHODS: Fourteen healthy male subjects underwent one simulated ECP procedure without reinfusion of buffy coats (BCs) in a two-center, open-label, prospective trial. Baseline peripheral blood BC, apheresis-separated untreated BC (BC1), and photoactivated BC (BC2) were evaluated in culture for viability by dye exclusion, apoptosis by annexin V binding, and cell proliferation response to phytohemagglutinin (PHA) stimulation by bromodeoxyuridine (BrdU) incorporation. RESULTS: Photoactivation (BC2) resulted in 88% expression of annexin V by Day 1 of culture compared with 37 and 39% for baseline and untreated BC1. Cell viability by propidium iodide exclusion was reduced to 10% in BC2 on Day 1 versus 65 and 60% for baseline and BC1. The proliferative response to PHA stimulation was 97% inhibited in the photoactivated BC2. CONCLUSIONS: These results demonstrate that the mechanical processes used for cell separation and processing of the BC in the absence of photoactivation do not induce a significant amount of apoptosis compared to the standard ECP with methoxsalen and UVA photoactivation.

Optimal Storage Conditions for Apheresis Research (OSCAR): a Biomedical Excellence for Safer Transfusion (BEST) Collaborative study.

BACKGROUND: Cell therapy products are often stored and transported between sites. The aim of this study was to determine the effect of storage temperature, solution, and cell concentration on nonmobilized, peripheral blood-derived mononuclear cells (MNCs). STUDY DESIGN AND METHODS: This was a multicenter prospective study involving healthy volunteers who underwent nonmobilized MNC collection by apheresis. Products were processed at local laboratories and concentrated to either 100 × 106 or 300 × 106 nucleated cells/mL in 5% human serum albumin (HSA) or HypoThermosol FRS (HT; BioLife Solutions). Products were stored at room temperature (RT; 20-25°C) or refrigerated temperatures (2-8°C) with assessment at 0, 24, 48, and 72 hours. NC and MNC concentration, viability, and flow cytometric analysis for CD3, CD4, CD8, CD14, CD19, CD25, and CD56 were measured. RESULTS: Viability decreased over time for all conditions tested. Refrigerated storage preserved viability greater than RT storage, especially for products with a higher cell concentration. RT maintenance with a high cell concentration was associated with a relative loss of CD14- and CD4-positive cells, whereas the concentration of cells positive for other markers tested did not vary. Finally, there was delayed decrease in pH when using HT compared with HSA; however, there was no difference in viability between the two solutions. CONCLUSION: Low cell concentrations (approx. 100 × 106 cells/mL), refrigerated temperatures, and HT storage solution appear to be the optimal conditions for storing nonmobilized, peripheral blood-derived MNC products.

Bacterial screening of apheresis platelets with a rapid test: a 113-month single center experience.

BACKGROUND: The 2016 Food and Drug Administration draft guidance describes the use of a rapid test (RT) to enhance platelet transfusion safety and availability. This study reports a 113-month experience of screening of apheresis platelets (APs) by RT. STUDY DESIGN AND METHODS: From July 2008 to October 2015, all APs underwent an RT on Day 4. Day 6 and 7 units were transfused with transfusion medicine physician approval. Any units remaining on Day 8 had a second RT performed. From November 2015 to November 2017, APs underwent an RT on Day 5 with a repeat RT on Days 6 and 7. During both periods, positive RTs underwent confirmatory testing with culture when repeat testing was positive. RESULTS: A total of 9009 APs underwent an RT on Day 4 or 5. Of these, 45 (0.5%) were RT positive, with no true positives. A total of 754 underwent a second RT on Day 8, with no positives. Since November 2015, 1152 platelets have undergone a second RT on Day 6; 391 have undergone a third RT on Day 7. Of these, five (0.4%) were RT positive on Day 6, with no true positives. There were no septic transfusion reactions identified by passive surveillance at our institution during either study period. CONCLUSION: To date, we have not detected any true positives after performing 11,306 tests on 9009 APs. A total of 1906 underwent testing twice, and 391 underwent testing three times. We did not identify any conversions from negative to positive on repeat testing.

Current practices for viability testing of cryopreserved cord blood products: an international survey by the cellular therapy team of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative.

BACKGROUND: Viability testing is a common practice in laboratories. The goal of this study was to ascertain current laboratory practices internationally for performing viability testing for cryopreserved cord blood (CB) products and glean information about how to standardize the method to improve interlaboratory reproducibility. STUDY DESIGN AND METHODS: A survey to evaluate current laboratory practices for viability testing was designed and distributed internationally. The question topics included sampling and testing methods, responses to unexpected results, and the rating of the reliability of the CB quality tests, together with expectations for standardization. RESULTS: There were 32 respondents to the survey, of whom 28 responded to the more detailed questionnaire about viability methods. Overall, responses indicated that various stains were used among the laboratories, and when multiple sites used the same viability stain the methods differed. The majority of the respondents were in favor of standardizing the viability testing methods. A wide variety of preferences were communicated about how to standardize the method, but a majority did advocate the use of 7-aminoactinomycin D (7-AAD) with flow cytometry. CONCLUSIONS: The survey results revealed a variety of tests and inconsistent interlaboratory practices for performing the viability assay. Flow cytometry with a 7-AAD dye was suggested as a first step toward standardization.

Safety and efficacy of cryopreserved platelets in bleeding patients with thrombocytopenia.

BACKGROUND: The short dating period of room temperature-stored platelets (PLTs; 5-7 days) limits their availability at far-forward combat facilities and at remote civilian sites in the United States. PLT cryopreservation in 6% DMSO and storage for up to 2 years may improve timely availability for bleeding patients. STUDY DESIGN AND METHODS: A dose escalation trial of DMSO-cryopreserved PLTs (CPPs) compared to standard liquid-stored PLTs (LSPs) was performed in bleeding patients with thrombocytopenia. Within each of four cohorts, six patients received escalating doses of CPP (0.5 unit, 1 unit, and sequential transfusions of 2 and 3 units) and one received a LSP transfusion. Patients were monitored for adverse events (AEs), coagulation markers, PLT responses, and hemostatic efficacy. RESULTS: Patients with a World Health Organization bleeding score of 2 or more received from 0.5 to 3 units of CPP (n = 24) or 1 unit of LSP (n = 4). There were no related thrombotic or other serious AEs experienced. Mild transfusion-related AEs of chills and fever (n = 1), transient increased respiratory rate (n = 1), DMSO-related skin odor (n = 2), and headache (n = 1) were observed after CPP transfusion. Among CPP recipients 14 of 24 (58%) had improved bleeding scores, including three of seven (43%) patients who had intracerebral bleeding. CPP posttransfusion PLT increments were significantly less than those of LSPs; however, days to next transfusion were the same. After transfusion, the CPP recipients had improvements in some variables of thrombin generation tests and thromboelastography. CONCLUSION: Cryopreserved PLT transfusions appear to be safe and effective when given to bleeding patients with thrombocytopenia.

Therapeutic plasma exchange for thrombotic thrombocytopenic purpura with refractory thrombocytopenia.

Thrombotic thrombocytopenic purpura (TTP) is an acute, life-threatening illness with disseminated platelet-rich thromboses of small vessels that variably presents with the classic clinical "pentad" of microangiopathic hemolytic anemia, thrombocytopenia, fever, altered mental status, and acute kidney injury. Most cases are caused by an acquired autoantibody to ADAMTS13, a metalloproteinase that cleaves large von Willebrand Factor (vWF) multimers. The mainstay of treatment is daily therapeutic plasma exchange (TPE), sometimes with adjunctive pharmacologic immunosuppression. TPE is generally continued until the platelet count is greater than 150 × 103 /µL and the lactate dehydrogenase is near normal for 2-3 consecutive days. Unfortunately, there is no clear guidance for when thrombocytopenia is refractory for a prolonged period of time. The following case describes such a scenario in which consecutive ADAMTS13 activity and inhibitor levels were used to guide the decision to stop treatment with TPE in a patient who failed to recover their platelet count.

Extracorporeal photopheresis for graft versus host disease: Identifying a clinical pathway and associated resource utilization.

Extracorporeal photopheresis (ECP) is an established therapy for the treatment of graft-versus-host-disease (GVHD) following an allogeneic stem cell transplant. We performed a prospective analysis of patients receiving ECP treatment for GVHD to identify a clinical pathway and resource utilization of this process. The cohort included consecutive allogeneic stem cell recipients with GVHD. ECP was performed using the CELLEX Photopheresis System or the UVAR XTS Photopheresis System (Therakos, Inc, Exton, PA). A clinical pathway was developed and a time and motion study was conducted to define the resource utilization and costs associated with ECP. Patients were treated with either CELLEX (n = 18 procedures) or UVAR (n = 4 procedures). Total time commitment for each procedure for the 2 machines differed. The time for ECP was 117 min (median, range: 91-164 min) using CELLEX and 161 min (median; range: 140-210) using the UVAR-XTS machine. Total costs of each ECP procedure were $3420.50. There is a considerable time commitment of the patient and the clinical staff when employing ECP to treat GVHD. ECP costs are significant considering this is a prolonged therapy continued for several months. With this finalized pathway and costs, we have a standardized clinical pathway for the treatment of GVHD. We are addressing minimizing resource utilization while emphasizing quality care for these patients.

Red blood cell metabolic responses to refrigerated storage, rejuvenation, and frozen storage.

BACKGROUND: Storage of red blood cells (RBCs) under blood bank conditions promotes metabolic modulation within the RBC. This "metabolic storage lesion" may affect the quality and safety of the transfused RBCs. The aim of this study is to determine the metabolic changes in stored RBCs over 42 days of routine storage followed by a US Food and Drug Administration-approved method of rejuvenation, freezing, and preparation for transfusion. STUDY DESIGN AND METHODS: We exploited a mass spectrometry-based metabolomics approach to monitor 42-day-stored citrate phosphate dextrose/AS-1 RBCs (n = 29) that were rejuvenated, glycerolized and frozen, then thawed and deglycerolized, and held for 24 hours at 1 to 6ºC in saline-glucose. RESULTS: Previously reported metabolic alterations were confirmed in 42-day-old RBCs. In this study, in total, 181 (62%) of the biochemical compounds exhibited significant (p ≤ 0.05) change compared with Day 0 values. Rejuvenation restored adenosine triphosphate and 2,3-diphosphoglycerate levels, replenished purine reservoirs, up regulated glycolysis, increased levels of pentose phosphate pathway intermediates, and partially rescued glutathione biosynthesis. Increased levels of lysophospholipid in rejuvenated RBCs suggests the activation of recycling pathways of damaged membrane lipids, in which a total of 167 (57%) biochemical compounds showed significant change compared with Day 42 values. CONCLUSION: Rejuvenation reversed over one-half of the metabolic biochemical compounds evaluated compared with Day 42 values, and the compounds were stable through frozen storage and preparation for transfusion. Rejuvenation promoted significant metabolic reprogramming, including the reactivation of energy-generating and antioxidant pathways (the pentose phosphate pathway and glutathione homeostasis), salvage reactions, cofactor reservoirs, and membrane lipid recycling.