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Abbreviations COVID-19 coronavirus disease 2019 IVIG intravenous immunoglobulin PDMPs plasma-derived medicinal products PPTA plasma protein therapeutics association Plasma-derived medicinal products (PDMPs) play an integral role in medical treatment and prophylaxis. Finally, regular healthy donor-derived IVIG has been proposed as a potential therapeutic option in patients with COVID-19 as well.25,26 All of these treatments acutely raise the demand for (convalescent) plasma. Under these circumstances, many investigational uses were limited, but also in approved key indications like primary immunodeficiency, painful restrictions, and modification of approved therapy had to be implemented.5 With the COVID-19 pandemic the global plasma supply has come under additional pressure. The donor pool has been reduced by COVID-19 infections or fear of exposure to COVD-19 in the collection center setting, and the number of collections per donor has suffered as well. [Extracted from the article]

Background: In experimental canine septic shock, depressed circulating granulocyte counts were associated with a poor outcome and increasing counts with prophylactic granulocyte colony-stimulating factor (G-CSF) improved outcome. Therapeutic G-CSF, in contrast, did not improve circulating counts or outcome, and therefore investigation was undertaken to determine whether transfusing granulocytes therapeutically would improve outcome.Study Design and Methods: Twenty-eight purpose-bred beagles underwent an intrabronchial Staphylococcus aureus challenge and 4 hours later were randomly assigned to granulocyte (40-100 × 109 cells) or plasma transfusion.Results: Granulocyte transfusion significantly expanded the low circulating counts for hours compared to septic controls but was not associated with significant mortality benefit (1/14, 7% vs. 2/14, 14%, respectively; p = 0.29). Septic animals with higher granulocyte count at 4 hours (median [interquartile range] of 3.81 3.39-5.05] vs. 1.77 [1.25-2.50]) had significantly increased survival independent of whether they were transfused with granulocytes. In a subgroup analysis, animals with higher circulating granulocyte counts receiving donor granulocytes had worsened lung injury compared to septic controls. Conversely, donor granulocytes decreased lung injury in septic animals with lower counts.Conclusion: During bacterial pneumonia, circulating counts predict the outcome of transfusing granulocytes. With low but normal counts, transfusing granulocytes does not improve survival and injures the lung, whereas for animals with very low counts, but not absolute neutropenia, granulocyte transfusion improves lung function. [ABSTRACT FROM AUTHOR]

Background: During sepsis, higher plasma cell-free hemoglobin (CFH) levels portend worse outcomes. In sepsis models, plasma proteins that bind CFH improve survival. In our canine antibiotic-treated Staphylococcus aureus pneumonia model, with and without red blood cell (RBC) exchange transfusion, commercial human haptoglobin (Hp) concentrates bound and compartmentalized CFH intravascularly, increased CFH clearance, and lowered iron levels, improving shock, lung injury, and survival. We now investigate in our model how very high CFH levels and treatment time affect Hp's beneficial effects.Materials and Methods: Two separate canine pneumonia sepsis Hp studies were undertaken: one with exchange transfusion of RBCs after prolonged storage to raise CFH to very high levels and another with rapidly lethal sepsis alone to shorten time to treat. All animals received continuous standard intensive care unit supportive care for 96 hours.Results: Older RBCs markedly elevated plasma CFH levels and, when combined with Hp therapy, created supraphysiologic CFH-Hp complexes that did not increase CFH or iron clearance or improve lung injury and survival. In a rapidly lethal bacterial challenge model without RBC transfusion, Hp binding did not increase clearance of complexes or iron or show benefits seen previously in the less lethal model.Discussion: High-level CFH-Hp complexes may impair clearance mechanisms and eliminate Hp's beneficial effect during sepsis. Rapidly lethal sepsis narrows the therapeutic window for CFH and iron clearance, also decreasing Hp's beneficial effects. In designing clinical trials, dosing and kinetics may be critical factors if Hp infusion is used to treat sepsis. [ABSTRACT FROM AUTHOR]

See editorial on page 2463–2463, in this issue [ABSTRACT FROM AUTHOR]

The public stakeholders were predominant members of the LGBTQ communities who regard this exclusion as class discrimination and remain understandably dismayed by the slow pace of change even as sensitive and specific screening tests have all but eliminated transfusion-associated HIV/AIDS. As I looked around the room, it dawned on me that most of the public stakeholders had not been born when that "new" disease now referred to as AIDS emerged, killed an estimated 12 000 transfusion recipients in the United States, and infected an estimated 2000 transfused Canadians with the human immune deficiency virus (HIV) between 1980 and 1985 [[1]]. As information accumulated indicting transfusion as a vector for HIV, well before the licensure of the first screening test in 1985, AIDS had been falsely labelled as the "gay disease". [Extracted from the article]

Background: Storage temperature is a critical factor for maintaining red-blood cell (RBC) viability, especially during prolonged cold storage. The target range of 1 to 6°C was established decades ago and may no longer be optimal for current blood-banking practices.Study Design and Methods: Human and canine RBCs were collected under standard conditions and stored in precision-controlled refrigerators at 2°C, 4°C, or 6°C.Results: During 42-day storage, human and canine RBCs showed progressive increases in supernatant non-transferrin-bound iron, cell-free hemoglobin, base deficit, and lactate levels that were overall greater at 6°C and 4°C than at 2°C. Animals transfused with 7-day-old RBCs had similar plasma cell-free hemoglobin and non-transferrin-bound iron levels at 1 to 72 hours for all three temperature conditions by chromium-51 recovery analysis. However, animals transfused with 35-day-old RBCs stored at higher temperatures developed plasma elevations in non-transferrin-bound iron and cell-free hemoglobin at 24 and 72 hours. Despite apparent impaired 35-day storage at 4°C and 6°C compared to 2°C, posttransfusion chromium-51 recovery at 24 hours was superior at higher temperatures. This finding was confounded by a preparation artifact related to an interaction between temperature and storage duration that leads to removal of fragile cells with repeated washing of the radiolabeled RBC test sample and renders the test sample unrepresentative of the stored unit.Conclusions: RBCs stored at the lower bounds of the temperature range are less metabolically active and produce less anaerobic acidosis and hemolysis, leading to a more suitable transfusion product. The higher refrigeration temperatures are not optimal during extended RBC storage and may confound chromium viability studies. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing allogeneic hematopoietic stem cell transplant require variable, often extensive transfusion support. Identification of factors that predict urgent, intensive, or special needs should improve management of these patients.Study Design and Methods: This is a retrospective study of red blood cell (RBC) and platelet transfusion support provided for sequential matched sibling donor allogeneic transplants conducted at the Clinical Center, National Institutes of Health, from 1993 through 2010. Factors potentially important for predicting quantity of RBC and platelet transfusions, and time to transfusion independence through Day 200 following hematopoietic stem cell transplantation were evaluated.Results: Subjects (n = 800) received 10,591 RBC and 10,199 platelet transfusions. Multivariable analysis demonstrated that the need for RBC pretransplant, CD34+ dose, transplant year, diagnostic category, and ABO match were significantly independently associated with quantity of RBC transfusions during Days 0 through 30. Only pretransplant need for RBCs, CD34+ dose, and transplant year had significance during Days 0 through 100. Similar analyses for quantity of platelet transfusions demonstrated that for both Days 0 through 30 and 0 through 100 significant factors were need for platelet support before transplant, CD34+ dose, transplant year, and transplant regimen. Of note, long term, during Days 101 through 200, only CD34+ dose remained significant for quantity of RBC and platelet transfusions. Analysis of time to transfusion independence demonstrated that patients with ABO major mismatches required longer to achieve freedom from RBC transfusion support compared to identical matches or those with minor mismatches.Conclusion: Patient-specific factors including CD34+ dose and ABO match of the graft should be given particular consideration by transfusion services when planning support of patients receiving allogeneic hematopoietic stem cell transplant. [ABSTRACT FROM AUTHOR]

Background: The 1000 Genomes Project provides a database of genomic variants from whole genome sequencing of 2504 individuals across five continental superpopulations. This database can enrich our background knowledge of worldwide blood group variant geographic distribution and identify novel variants of potential clinical significance.Study Design and Methods: The 1000 Genomes database was analyzed to 1) expand knowledge about continental distributions of known blood group variants, 2) identify novel variants with antigenic potential and their geographic association, and 3) establish a baseline scaffold of chromosomal coordinates to translate next-generation sequencing output files into a predicted red blood cell (RBC) phenotype.Results: Forty-two genes were investigated. A total of 604 known variants were mapped to the GRCh37 assembly; 120 of these were reported by 1000 Genomes in at least one superpopulation. All queried variants, including the ACKR1 promoter silencing mutation, are located within exon pull-down boundaries. The analysis yielded 41 novel population distributions for 34 known variants, as well as 12 novel blood group variants that warrant further validation and study. Four prediction algorithms collectively flagged 79 of 109 (72%) known antigenic or enzymatically detrimental blood group variants, while 4 of 12 variants that do not result in an altered RBC phenotype were flagged as deleterious.Conclusion: Next-generation sequencing has known potential for high-throughput and extended RBC phenotype prediction; a database of GRCh37 and GRCh38 chromosomal coordinates for 120 worldwide blood group variants is provided as a basis for this clinical application. [ABSTRACT FROM AUTHOR]

Background: No studies have been performed comparing intravenous (IV) iron with transfused red blood cells (RBCs) for treating anemia during infection. In a previous report, transfused older RBCs increased free iron release and mortality in infected animals when compared to fresher cells. We hypothesized that treating anemia during infection with transfused fresh RBCs, with minimal free iron release, would prove superior to IV iron therapy.Study Design and Methods: Purpose-bred beagles (n = 42) with experimental Staphylococcus aureus pneumonia rendered anemic were randomized to be transfused RBCs stored for 7 days or one of two IV iron preparations (7 mg/kg), iron sucrose, a widely used preparation, or ferumoxytol, a newer formulation that blunts circulating iron levels.Results: Both irons increased the alveolar-arterial oxygen gradient at 24 to 48 hours (p = 0.02-0.001), worsened shock at 16 hours (p = 0.02-0.003, respectively), and reduced survival (transfusion 56%; iron sucrose 8%, p = 0.01; ferumoxytol 9%, p = 0.04). Compared to fresh RBC transfusion, plasma iron measured by non-transferrin-bound iron levels increased with iron sucrose at 7, 10, 13, 16, 24, and 48 hours (p = 0.04 to p < 0.0001) and ferumoxytol at 7, 24, and 48 hours (p = 0.04 to p = 0.004). No significant differences in cardiac filling pressures or performance, hemoglobin (Hb), or cell-free Hb were observed.Conclusions: During canine experimental bacterial pneumonia, treatment of mild anemia with IV iron significantly increased free iron levels, shock, lung injury, and mortality compared to transfusion of fresh RBCs. This was true for iron preparations that do or do not blunt circulating free iron level elevations. These findings suggest that treatment of anemia with IV iron during infection should be undertaken with caution. [ABSTRACT FROM AUTHOR]

Background: Acquired copy-neutral loss of heterozygosity has been described in myeloid malignant progression with an otherwise normal karyotype.Case Report: A 65-year-old woman with MPL-mutated essential thrombocythemia and progression to myelofibrosis was noted upon routine pretransplant testing to have mixed field reactivity with anti-D and an historic discrepancy in RhD type. The patient had never received transfusions or transplantation.Results: Gel immunoagglutination revealed group A red blood cells and a mixed-field reaction for the D phenotype, with a predominant D-negative population and a small subset of circulating red blood cells carrying the D antigen. Subsequent genomic microarray single nucleotide polymorphism profiling revealed copy-neutral loss of heterozygosity of chromosome 1 p36.33-p34.2, a known molecular mechanism underlying fibrotic progression of MPL-mutated essential thrombocythemia. The chromosomal region affected by this copy-neutral loss of heterozygosity encompassed the RHD, RHCE, and MPL genes. We propose a model of chronological molecular events that is supported by RHD zygosity assays in peripheral lymphoid and myeloid-derived cells.Conclusion: Copy-neutral loss of heterozygosity events that lead to clonal selection and myeloid malignant progression may also affect the expression of adjacent unrelated genes, including those encoding for blood group antigens. Detection of mixed-field reactions and investigation of discrepant blood typing results are important for proper transfusion support of these patients and can provide useful surrogate markers of myeloproliferative disease progression. [ABSTRACT FROM AUTHOR]

Plasma-derived medicinal products (PDMPs) such as immunoglobulins and clotting factors are listed by the World Health Organization as essential medicines. These and other PDMPs are crucial for the prophylaxis and treatment of patients with bleeding disorders, immune deficiencies, autoimmune and inflammatory diseases, and a variety of congenital deficiency disorders. While changes in clinical practice in developed countries have reduced the need for red blood cell transfusions thereby significantly reducing the collection volumes of whole blood and recovered plasma suitable for fractionation, the need for PDMPs worldwide continues to increase. The majority of plasma supplies for the manufacture of PDMPs is met by the US commercial plasma industry. However, geographic imbalance in the collection of plasma raises concerns that local disruptions of plasma supplies could result in regional and global shortages of essential PDMPs. Plasma, which fits the definition of a strategic resource, that is, "an economically important raw material which is subject to a higher risk of supply interruption," should be considered a strategic resource comparable to energy and drinking water. Plasma collections should be increased outside the United States, including in low- and middle-income countries. The need for capacity building in these countries is an essential part to strengthen quality plasma collection. This will require changes in national and regional policies. We advocate the need for the restoration of an equitable balance of the international plasma supply to reduce the risk of supply shortages worldwide. Strategic independence of plasma should be endorsed on a global level. [ABSTRACT FROM AUTHOR]

The authors comment on the presence of red blood cell (RBC) storage lesion. Topics covered include the efficacy and safety as two major concerns regarding stored RBC, the requirements of the U.S. Food and Drug Administration (FDA) on RBC biopreservation, and the association of stored RBC to more clinical adverse effects, and how to best evaluate the therapeutic effectiveness of RBC transfusions of any storage duration.

Background: In canine models, transfused older stored red blood cells (RBCs) hemolyze in vivo resulting in significantly increased intravascular cell-free hemoglobin (CFH) and non-transferrin-bound iron (NTBI). During canine bacterial pneumonia with septic shock, but not in controls, older stored RBCs were associated with significantly increased lung injury and mortality. It is unknown if in shock without infection transfusion of older RBCs will result in similar adverse effects.Study Design and Methods: Two-year-old purpose-bred beagles (n = 12) were transfused similar quantities of either older (42-day) or fresher (7-day) stored universal donor canine RBCs 2.5 hours after undergoing controlled hemorrhage (55 mL/kg).Results: With older transfused RBCs, CFH (p < 0.0001) and NTBI (p = 0.004) levels increased, but lung injury (p = 0.01) and C-reactive protein levels (p = 0.002) declined and there was a trend toward lower mortality (18% vs. 50%). All three deaths after transfused fresher RBCs resulted from hepatic fractures. Lowered exogenous norepinephrine requirements (p < 0.05) and cardiac outputs (p < 0.05) after older transfused RBCs were associated with increased CFH levels that have known vasoconstrictive nitric oxide scavenging capability.Conclusions: In hemorrhagic shock, older RBCs altered resuscitation physiology but did not worsen clinical outcomes. Elevated CFH may lower norepinephrine requirements and cardiac outputs ameliorating reperfusion injuries. With hemorrhagic shock, NTBI levels persist in contrast to the increased clearance, lung injury, and mortality in the previously reported infection model. These preclinical data suggest that whereas iron derived from older RBCs promotes bacterial growth, worsening septic shock mortality during infection, release of CFH and NTBI during hemorrhagic shock is not necessarily harmful. [ABSTRACT FROM AUTHOR]

Background: Massive exchange transfusion of 42-day-old red blood cells (RBCs) in a canine model of Staphylococcus aureus pneumonia resulted in in vivo hemolysis with increases in cell-free hemoglobin (CFH), transferrin-bound iron (TBI), non-transferrin-bound iron (NTBI), and mortality. We have previously shown that washing 42-day-old RBCs before transfusion significantly decreased NTBI levels and mortality, but washing 7-day-old RBCs increased mortality and CFH levels. We now report the results of altering volume, washing, and age of RBCs.Study Design and Methods: Two-year-old purpose-bred infected beagles were transfused with increasing volumes (5-10, 20-40, or 60-80 mL/kg) of either 42- or 7-day-old RBCs (n = 36) or 80 mL/kg of either unwashed or washed RBCs with increasing storage age (14, 21, 28, or 35 days; n = 40).Results: All volumes transfused (5-80 mL/kg) of 42-day-old RBCs resulted in alike (i.e., not significantly different) increases in TBI during transfusion as well as in CFH, lung injury, and mortality rates after transfusion. Transfusion of 80 mL/kg RBCs stored for 14, 21, 28, and 35 days resulted in increased CFH and NTBI in between levels found at 7 and 42 days of storage. However, washing RBCs of intermediate ages (14-35 days) does not alter NTBI and CFH levels or mortality rates.Conclusions: Preclinical data suggest that any volume of 42-day-old blood potentially increases risks during established infection. In contrast, even massive volumes of 7-day-old blood result in minimal CFH and NTBI levels and risks. In contrast to the extremes of storage, washing blood stored for intermediate ages does not alter risks of transfusion or NTBI and CFH clearance. [ABSTRACT FROM AUTHOR]

Background In experimental pneumonia we found that transfused older blood increased mortality and lung injury that was associated with increased in vivo hemolysis and elevated plasma cell-free hemoglobin ( CFH), non-transferrin-bound iron ( NTBI), and plasma labile iron ( PLI) levels. In this study, we additionally analyze identically treated animals that received lower or higher bacterial doses. Study Design and Methods Two-year-old purpose-bred beagles (n = 48) challenged intrabronchially with Staphylococcus aureus (0 [n = 8], 1.0 × 109 [n = 8], 1.25 × 109 [n = 24], and ≥1.5 × 109 [n = 8] colony-forming units/kg) were exchange transfused with either 7- or 42-day-old canine universal donor blood (80 mL/kg in four divided doses). Results The greater increases in CFH with older blood over days after exchange proved relatively independent of bacterial dose. The lesser increases in CFH observed with fresher blood were bacterial dose dependent potentially related to bacterial hemolysins. Without bacterial challenge, levels of CFH, NTBI, and PLI were significantly higher with older versus fresher blood transfusion but there was no significant measurable injury. With higher-dose bacterial challenge, the elevated NTBI and PLI levels declined more rapidly and to a greater extent after transfusion with older versus fresher blood, and older blood was associated with significantly worse shock, lung injury, and mortality. Conclusion The augmented in vivo hemolysis of transfused older red blood cells ( RBCs) appears to result in excess plasma CFH and iron release, which requires the presence of established infection to worsen outcome. These data suggest that transfused older RBCs increase the risks from infection in septic subjects. [ABSTRACT FROM AUTHOR]

Red blood cells ( RBCs) degrade progressively during the weeks of refrigerated storage. No universally accepted definition of 'fresh' or 'old' RBCs exists. While practices vary from country to country, preservative solutions permitting shelf life as long as 7 weeks have been licenced. Transfusion of stored RBCs, particularly those at the end of the approved shelf life, has been implicated in adverse clinical outcomes. The results of observational analyses, animal models and studies in volunteers have proved provocative, controversial and contradictory. A recently completed randomized controlled trial ( RCT) in premature infants exemplifies the difficulties with moderately sized clinical studies. Several other RCTs are in progress. The effect of RBC storage may well vary according to the clinical setting. Resolution of the importance of the storage lesion may require large pragmatic clinical trials. In the meantime, institutions involved in blood collection and transfusion should explore strategies that assure blood availability, while limiting the use of the oldest RBCs currently approved by regulation. [ABSTRACT FROM AUTHOR]

In this article, the authors discuss changes in Blood system since the recognition of transfusion-associated AIDS. They state that it has been thirty years since the discovery of human immuno-deficiency virus (HIV) and it was originally known as lymphadenopathy-associated virus or human T-lymphotropic virus Type 3 (HTLV-III). They mention that federal response to transfusion-transmitted infections changed significantly after HIV emerged as a transfusion-transmitted infection.

The article focuses on a report by the U.S. Institute of Medicine regarding steps taken by the government and the private sector, and stakeholders to prevent the spread of human immunodeficiency virus and its impact on blood safety. It informs that blood banks in the San Francisco bay area implemented surrogate tests which included the assessment of the ratio of T-cell helper and suppressor cells.

BACKGROUND: Although transmission of Plasmodium falciparum (Pf) infection during red blood cell (RBC) transfusion from an infected donor has been well documented, malaria parasites are not known to infect hematopoietic stem cells. We report a case of Pf infection in a patient 11 days after peripheral blood stem cell transplant for sickle cell disease. STUDY DESIGN AND METHODS: Malaria parasites were detected in thick blood smears by Giemsa staining. Pf HRP2 antigen was measured by enzyme-linked immunosorbent assay on whole blood and plasma. Pf DNA was detected in whole blood and stem cell retention samples by real-time polymerase chain reaction using Pf species-specific primers and probes. Genotyping of eight Pf microsatellites was performed on genomic DNA extracted from whole blood. RESULTS: Pf was not detected by molecular, serologic, or parasitologic means in samples from the recipient until Day 11 posttransplant, coincident with the onset of symptoms. In contrast, Pf antigen was retrospectively detected in stored plasma collected 3 months before transplant from the asymptomatic donor. Pf DNA was detected in whole blood from both the donor and the recipient after transplant, and genotyping confirmed shared markers between donor and recipient Pf strains. Lookback analysis of RBC donors was negative for Pf infection. CONCLUSIONS: These findings are consistent with transmission by the stem cell product and have profound implications with respect to the screening of potential stem cell donors and recipients from malaria-endemic regions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Blood for transfusion is stored for up to 42 days. Older blood develops lesions and accumulates potentially injurious substances. Some studies report increasing toxicity as blood ages. We assessed the safety of transfused older versus newer stored blood. STUDY DESIGN AND METHODS: PubMed, Scopus, and Embase were searched using terms new and old and red blood cell and storage through May 6, 2011, for observational and randomized controlled studies comparing outcomes using transfused blood having longer and shorter storage times. Death was the outcome of interest. RESULTS: Twenty-one studies were identified, predominantly in cardiac surgery (n = 6) and trauma (n = 6) patients, including 409,966 patients. A test for heterogeneity of these studies' results was not significant for mortality (I2 = 3.7%, p = 0.41). Older blood was associated with a significantly increased risk of death (odds ratio, 1.16; 95% confidence interval [CI], 1.07-1.24). Using available mortality data, 97 (95% CI, 63-199) patients need to be treated with only new blood to save one life. Subgroup analysis of these trials indicated that the increased risk was not restricted to a particular type of patient, size of trial, or amount of blood transfused. CONCLUSION: Based on available data, use of older stored blood is associated with a significantly increased risk of death. [ABSTRACT FROM AUTHOR]

BACKGROUND: Spray-drying techniques are commonly utilized in the pharmaceutical, dairy, and animal feed industries for processing liquids into powders but have not been applied to human blood products. Spray-dried protein products are known to maintain stability during storage at room temperature. STUDY DESIGN AND METHODS: Plasma units collected at the donor facility were shipped overnight at room temperature to a processing facility where single-use spray drying occurred. After 48 hours' storage at room temperature, the spray-dried plasma product was split in two and rehydrated with 1.5% glycine or deionized water and assayed for chemistry analytes and coagulation factors. Matched fresh-frozen plasma was analyzed in parallel as controls. RESULTS: Reconstitution was achieved for both rehydration groups within 5 minutes (n = 6). There was no significant intergroup difference in recovery for total protein, albumin, immunoglobulin (Ig)G, IgA, and IgM (96% or higher). With the exception of Factor VIII (58%), the recovery of clotting factors in the glycine reconstituted products ranged from 72% to 93%. Glycine reconstitution was superior to deionized water. CONCLUSION: We documented proteins and coagulation activities were recovered in physiologic quantities in reconstituted spray-dried plasma products. Further optimization of the spray-drying method and reconstitution fluid may result in even better recoveries. Spray drying is a promising technique for preparing human plasma that can be easily stored at room temperature, shipped, and reconstituted. Rapid reconstitution of the microparticles results in a novel plasma product from single donors. [ABSTRACT FROM AUTHOR]

The article offers information on the report of American Association of Blood Banks (AABB) on Xenotropic murine leukemia virus-related virus (XMRV) and blood transfusion. It states that AABB formed an Interorganizational Task Force, which studuied previous reports on XMRV and blood donation. It mentions that several previous reports identified the evidence of infection with XMRV in the blood of the patients diagnosed with chronic fatigue syndrome (CFS).

To determine the prevalence and impact of transfusing plasma containing white blood cell antibodies, we compared two high-throughput HLA antibody screening assays and prospectively examined the medical records of all platelet (PLT) recipients to detect subtle manifestations of transfusion-related acute lung injury and other transfusion reactions. Serum samples from 136 plateletpheresis donors were tested for HLA Class I and II antibodies using microbead (LABScreen PRA, One Lambda) and microchip (Dynachip, Invitrogen) assays. Electronic medical records of all recipients were reviewed for vital signs and nursing documentation before and after transfusion. In the microchip assay with a cutoff value of 0.25, 2.9% of samples were positive for Class I and 8.9% for Class II antibodies; with a cutoff value of 0.1, the results were 14.9 and 21.6%, respectively. In the microbead assay (normalized background ratio, 1.5), 15% were positive for Class I and 21% for Class II antibodies. The prevalence of HLA antibodies was 17% in donors without pregnancy or transfusion history and 47% in donors with such history. The PLTs were transfused in 265 episodes to 67 patients. There were no reported reactions; however, symptoms or vital sign changes were noted in seven transfusion episodes. The incidence of reactions was 2.7% (2/75) for antibody-positive units and 2.6% (5/190) for antibody-negative units. Microbead and microchip assays yielded similar results. The prevalence of HLA antibodies was greater in donors with a history of pregnancy or transfusion, but no increase in the incidence of transfusion reactions was noted in recipients of components from donors with HLA antibodies. [ABSTRACT FROM AUTHOR]

The author reflects on the expanding use of human blood and blood products in the U.S. resulted from the development of scientific knowledge on the use of blood in medical treatment. He highlights the establishment of a complex of organizations that collect, process, and distribute blood and its products as well as the nation's growing blood resource.

In July 2008, a workshop sponsored by the Division of Blood Diseases and Resources of the National Heart, Lung, and Blood Institute (NHLBI) was convened to identify potential research opportunities that could advance our understanding of both the biologic and the clinical impact of the various available pathogen reduction/inactivation (PR/PI) methods of blood components (platelets [PLTs], red blood cells, and plasma) intended for allogeneic transfusion. These discussions resulted in consensus that, even though several PR/PI technologies have already been licensed and are being used in Europe and elsewhere for PLTs and plasma, concerns about possible side effects, particularly component quality and pulmonary toxicity, have impeded regulatory approval in North America (United States and Canada). Such concerns thus threaten to stall further development of these technologies. As a consequence, the NHLBI workshop participants focused on formulating a series of research-related recommendations to better understand, mitigate, and prevent these adverse effects. Other important issues identified included the need for a single method to inactivate pathogens in whole blood without damaging the various blood components; new ways to monitor the efficacy of treated components, including animal models to screen for safety; a better understanding of the effect of PR/PI-treated products on recipient alloimmunization, tolerance, and immune modulation; understanding the impact of PR/PI on various other noninfectious hazards of transfusion; and establishing methods to evaluate risk-benefit and cost-effectiveness, in particular with reference to emerging pathogens. The working group also discussed issues related to specific blood components, such as improving the process of clinical evaluation, investigating the impact of PR/PI on component storage lesions, understanding mechanisms that reduce component viability, and addressing the underlying resistance to the adoption of PR/PI-treated components. This communication summarizes the opinions of workshop participants on these issues and concludes with a list of areas for possible research that could advance the application of PR/PI methods to enhance the safety of the world's blood supplies. [ABSTRACT FROM AUTHOR]