Clinical and economic impacts of large volume delayed sampling and pathogen reduction technology platelet processing strategies in the United States.

BACKGROUND: Large volume delayed sampling (LVDS) and pathogen reduction technology (PRT) are strategies for platelet processing to minimize transfusion of contaminated platelet components (PCs). This study holistically compares the economic and clinical impact of LVDS and PRT in the United States. STUDY DESIGN AND METHODS: A decision model was constructed to simulate collection, processing, and use of PCs and to compare processing strategies: PRT with 5-day shelf life, LVDS with 7-day shelf life (LVDS7), and LVDS with 5-day shelf life extended to 7 days with secondary testing (LVDS5/2). Target population was adults requiring two or more transfusions. Collection, processing, storage, and distribution data were obtained from the National Blood Collection and Utilization Survey and published literature. Patient outcomes associated with transfusions were obtained from AABB guidelines, meta-analyses, and other published clinical studies. Costs were obtained from reimbursement schedules and other published sources. RESULTS: Given 10,000 donated units, 9512, 9511, and 9651 units of PRT, LVDS5/2, and LVDS7 PCs were available for transfusion, respectively. With these units, 1502, 2172, and 2329 transfusions can be performed with similar levels of adverse events. Assuming 30 transfusions a day, a hospital would require 69,325, 47,940, and 45,383 units of PRT, LVDS5/2, and LVDS7 platelets to perform these transfusions. The mean costs to perform transfusions were significantly higher with PRT units. CONCLUSIONS: Compared with PRT, LVDS strategies were associated with lower costs and higher PC availability while patients experienced similar levels of adverse events. Increased utilization of LVDS has the potential to improve efficiency, expand patient access to platelets, and reduce health care costs.

Pathogen reduction of whole blood: Supplementing fibrinogen partly corrects clot formation in a massive transfusion model.

BACKGROUND: The use of whole blood (WB) to treat trauma patients is becoming more common. Similar to the treatment of individual components, pathogen inactivation (PI) technologies are available to treat WB. The impact of PI on WB function is not well understood. This study investigated the impact of PI of WB with riboflavin/ultraviolet (UV) light on its hemostatic function by modeling transfusion scenarios for trauma patients and assessing transfusion efficacy by rotational thromboelastometry (ROTEM). As fibrinogen is affected by PI of WB, the effect of fibrinogen supplementation commonly used in trauma patients was also analyzed in this model. STUDY DESIGN AND METHODS: Trauma transfusion scenarios were simulated by mixing untreated WB or WB treated with the Mirasol PI technology (riboflavin/UV) in different ratios with hemodiluted blood, and the thromboelasticity was monitored by ROTEM. The impact of supplementation with the fibrinogen concentrate RiaSTAP was investigated in this model. RESULTS: Pathogen-inactivated WB (PI-WB) showed decreased activity in the hemostatic profile compared to the untreated control. Hemodiluted blood at a hematocrit (hct) of 20%, which was reconstituted with PI-WB or untreated WB, exhibited increased alpha values, maximum clot firmness, and clot formation time. Simulating transfusion scenarios by blood replacement with PI-WB resulted in a significant difference in ROTEM parameters between reconstituted PI-treated and -untreated WB (p ≥ .05). The effect of PI treatment waned when PI-WB was enriched with fibrinogen. CONCLUSION: ROTEM investigations suggest that PI treatment has a negative impact on WB clot formation unless fibrinogen supplementation is used.

Mitigation strategies for anti-D alloimmunization by platelet transfusion in haematopoietic stem cell transplant patients: a survey of NCCN® centres.

BACKGROUND AND OBJECTIVES: D-negative patients are at risk of developing an alloantibody to D (anti-D) if exposed to D during transfusion. The presence of anti-D can lead to haemolytic transfusion reactions and haemolytic disease of the newborn. Anti-D alloimmunization can also complicate allogeneic haematopoietic stem cell transplantation (HSCT) with haemolysis and increased transfusion requirements. The goal of this study was to determine whether cancer centres have transfusion practices intended to prevent anti-D alloimmunization with special attention in patients considered for HSCT. METHODS AND MATERIALS: To understand transfusion practices regarding D-positive platelets in D-negative patients with large transfusion needs, we surveyed the 28 cancer centres that are members of the National Comprehensive Cancer Network® (NCCN® ). RESULTS: Nineteen centres responded (68%). Most centres (79%) avoid transfusing D-positive platelets to RhD-negative patients when possible. Four centres (21%) avoid D-positive platelets only in D-negative women of childbearing age. If a D-negative patient receives a D-positive platelet transfusion, 53% of centres would consider treating with Rh immune globulin (RhIg) to prevent alloimmunization in women of childbearing age. Only one centre also gives RhIg to all D-negative patients who are HSCT candidates including adult men and women of no childbearing age. CONCLUSION: There is wide variation in platelet transfusion practices for supporting D-negative patients. The majority of centres do not have D-positive platelet transfusion policies focused on preventing anti-D alloimmunization specifically in patients undergoing HSCT. Multicentre, longitudinal studies are needed to understand the clinical implications of anti-D alloimmunization in HSCT patients.

Is there a risk of transfusion-transmissible infections after percutaneous needle treatments in blood donors? A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: The donor medical questionnaire identifies a blood donor's history of known blood safety risks. Current Australian, Canadian, European and USA legislation temporarily defers blood donors who received different percutaneous needle treatments (i.e. tattooing, acupuncture and piercing) from blood donation. This systematic review aimed to scientifically underpin these deferrals by identifying the best available evidence on the association between percutaneous needle treatments and the risk of transfusion-transmissible infections (TTIs). MATERIALS AND METHODS: Studies from three databases investigating the link between percutaneous needle treatments and TTIs (HBV, HCV and HIV infection) in blood donors were retained and assessed on eligibility by two reviewers independently. The association between percutaneous needle treatments and TTIs was expressed by conducting meta-analyses and calculating pooled effect measures (odds ratios (ORs) and 95% CIs). The GRADE methodology (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the quality of evidence. RESULTS: We identified 1242 references and finally included 21 observational studies. Twenty studies assessed the link between percutaneous needle treatments and HCV infection and found that blood donors receiving these treatments had an increased risk of HCV infection (tattooing: pooled OR 5·28, 95% CI [4·33, 6·44], P < 0·00001 (low-quality evidence); acupuncture: pooled OR 1·56, 95% CI [1·17, 2·08], P = 0·03 (very low-quality evidence); and piercing: pooled OR 3·25, 95% CI [1·68, 6·30], P = 0·0005 (low-quality evidence)). CONCLUSION: Percutaneous needle treatments may be associated with an increased HCV infection risk. Further high-quality studies are required to formulate stronger evidence-based recommendations on percutaneous needle treatments as a blood donor deferral criterion.

Screening the Blood Supply for Zika Virus in the 50 U.S. States and Puerto Rico: A Cost-Effectiveness Analysis.

Background: In 2016, universal individual donation nucleic acid testing (ID-NAT) of donated blood for Zika virus began in U.S. states and territories. Objective: To assess the cost-effectiveness of universal ID-NAT in the first year of screening compared with alternatives for the 50 states and separately for Puerto Rico. Design: Microsimulation that captured Zika-related harms to transfusion recipients, sexual partners, and their infants. Data Sources: National testing results compiled by AABB and costs, utilities, and outcome probabilities estimated from the literature. Target Population: Transfusion recipients. Time Horizon: Lifetime. Perspective: Societal. Intervention: Universal ID-NAT, universal mini-pool NAT (MP-NAT), and ID-NAT exclusively for components transfused to women of childbearing age. Seasonally targeted strategies in Puerto Rico and geographically targeted strategies in the 50 states were also considered. Outcome Measures: Costs, quality-adjusted life-years (QALYs), and outcomes. Results of Base-Case Analysis: In Puerto Rico, MP-NAT exclusively during high mosquito season was cost-effective at $81 123 per QALY (95% CI, -$49 138 to $978 242 per QALY). No screening policy was cost-effective in the 50 states. Universal ID-NAT cost $341 million per QALY (CI, $125 million to $2.90 billion per QALY) compared with no screening in the 50 states. Results of Sensitivity Analysis: In Puerto Rico, MP-NAT only during the season of high mosquito activity was most cost-effective in 64% of probabilistic sensitivity analysis iterations. In the 50 states, no intervention was cost-effective in 99.99% of iterations. Cost-effectiveness was highly dependent on the rate of assumed infectious donations. Limitation: Data were limited on the component-specific transmissibility of Zika and long-term sequelae of infection. Conclusion: Screening was cost-effective only in the high mosquito season in Puerto Rico, and no evaluated screening policy was cost-effective in the 50 states. During periods with lower rates of Zika-infectious donations, the cost-effectiveness of screening will be even less favorable. Primary Funding Source: None.

Obstetric intra-operative cell salvage and maternal fetal red cell contamination.

BACKGROUND: The significance of fetal red blood cell (RBC) contamination in obstetric intra-operative cell salvage is not fully known. It is unclear if we re-infuse a larger volume of fetal RBCs into the maternal circulation than the amount that occurs secondary to transplacental haemorrhages is unclear. We also do not know if there is a critical volume required to cause alloimmunisation or if larger volumes increase the risk. OBJECTIVES: The aim of this study is to provide data on the level of fetal RBC contamination in the maternal circulation prior to delivery and immediately post-partum and to compare these levels to those found in processed cell-salvaged blood. METHODS: In the first part of this study, we quantified the levels of fetal RBCs circulating in women immediately prior to delivery. This was then repeated with a separate group measuring the levels of fetal RBCs pre- and post-delivery. RESULTS: We found that 37% of women had fetal cells detected in their circulation, median 0·00 mL (IQR 0-0·24; average 0·3 mL, maximum 4·56 mL). Fetal RBCs were present pre-delivery (maximum 0·66 mL) in 16% of women, increasing to 53% post-delivery (median 0·66 mL; IQR 0·22-2·20, maximum 21·20 mL). CONCLUSIONS: We have shown that fetal RBCs are present in the maternal circulation throughout pregnancy and that the volumes are comparable to that obtained from intra-operative salvage, with contamination amounts of up to 19 mL. At the Royal Cornwall Hospital, our experience and evidence supports offering intra-operative salvage to all women, and we have not noted an increase in antibody formation, compared to allogeneic transfusion.

Evidence and the Politics of Deimplementation: The Rise and Decline of the "Counseling and Testing" Paradigm for HIV Prevention at the US Centers for Disease Control and Prevention.

POLICY POINTS: In situations of scientific uncertainty, public health interventions, such as counseling for HIV infection, sometimes must be implemented before obtaining evidence of efficacy. The history of HIV counseling and testing, which served as the cornerstone of HIV prevention efforts at the US Centers for Disease Control and Prevention (CDC) for a quarter of a century, illustrates the influence of institutional resistance on public health decision making and the challenge of de-implementing well-established programs. CONTEXT: In 1985, amid uncertainty about the accuracy of the new test for HIV, public health officials at the Centers for Disease Control and Prevention (CDC) and AIDS activists agreed that counseling should always be provided both before and after testing to ensure that patients were tested voluntarily and understood the meaning of their results. As the "exceptionalist" perspective that framed HIV in the early years began to recede, the purpose of HIV test counseling shifted over the next 30 years from emphasizing consent, to providing information, to encouraging behavioral change. With this increasing emphasis on prevention, HIV test counseling faced mounting doubts about whether it "worked." The CDC finally discontinued its preferred test counseling approach in October 2014. METHODS: Drawing on key informant interviews with current and former CDC officials, behavioral scientists, AIDS activists, and others, along with archival material, news reports, and scientific and governmental publications, we examined the origins, development, and decline of the CDC's "counseling and testing" paradigm for HIV prevention. FINDINGS: Disagreements within the CDC emerged by the 1990s over whether test counseling could be justified on the basis of efficacy and cost. Resistance to the prospect of policy change by supporters of test counseling in the CDC, gay activists for whom counseling carried important ethical and symbolic meanings, and community organizations dependent on federal funding made it difficult for the CDC to de-implement the practice. CONCLUSIONS: Analyses of changes in public health policy that emphasize the impact of research evidence produced in experimental or epidemiological inquiries may overlook key social and political factors involving resistance to deimplementation that powerfully shape the relationship between science and policy.

Evaluation of the tolerability and immunogenicity of ultraviolet C-irradiated autologous platelets in a dog model.

BACKGROUND: The THERAFLEX ultraviolet (UV) platelets (PLTs) pathogen reduction system for PLT concentrates (PCs) operates using ultraviolet C (UVC) light at a wavelength of 254 nm. UVC treatment can potentially alter proteins, which may affect drug tolerance in humans and influence the immunogenicity of blood products. This preclinical study in beagle dogs was designed to evaluate the safety pharmacology of UVC-irradiated PCs after intravenous administration and to determine whether they are capable of eliciting humoral responses to PLTs and plasma proteins. STUDY DESIGN AND METHODS: Six beagle dogs each were transfused once every other week for 10 weeks with UVC-irradiated or nonirradiated PCs. All PCs were autologous canine single-donor products prepared from whole blood. Safety pharmacology variables were regularly assessed. The impact of UVC irradiation on PLT and plasma proteomes was analyzed by one- and two-dimensional gel electrophoresis. Serum samples were tested for UVC-induced antibodies by Western blot and flow cytometry. RESULTS: Dogs transfused with UVC-irradiated PCs showed no signs of local or systemic intolerance. Few but significant changes in PLT protein integrity were observed after UVC irradiation. Even after repeated administration of UVC-irradiated PCs, no antibodies against UVC-exposed plasma or PLT proteins were detected. CONCLUSIONS: Repeated transfusions of autologous UVC-treated PCs were well tolerated in all dogs studied. UVC irradiation did not cause significant plasma or PLT protein modifications capable of inducing specific antibody responses in the dogs. High-resolution proteomics combined with antibody analysis introduces a comprehensive and sensitive method for screening of protein modifications and antibodies specific for pathogen reduction treatment.

Infusion of P-Capt prion-filtered red blood cell products demonstrate acceptable in vivo viability and no evidence of neoantigen formation.

BACKGROUND: Transmission of variant Creutzfeldt-Jacob disease (vCJD) is a major concern in blood transfusion. The P-Capt filter has been shown to remove around 4 log ID(50) prion infectivity from prion-spiked human red blood cells (RBCs). STUDY DESIGN AND METHODS: Two independent, single-center, randomized, open-label studies were designed to analyze the safety of P-Capt-filtered RBCs. RBCs prepared from leukoreduced whole blood from 43 eligible subjects were randomly assigned to P-Capt filtration and/or storage in plasma or SAGM and stored for 28 or 42 days. Stored RBCs were analyzed for in vivo 24-hour recovery, hemolysis, metabolic variables, blood group antigen expression, neoantigen formation, and safety after autologous infusion. RESULTS: Mean P-Capt filtration times for leukoreduced RBCs were 41 (SAGM) to 51 (plasma) minutes. Thirteen of 14 subjects receiving P-Capt-filtered RBCs had 24-hour RBC recoveries of 75% or more after 42-day storage, with a mean hemolysis of less than 0.6%. No loss of RBC antigen expression or formation of neoantigens was observed. In both studies, RBCs had white blood cell counts of less than 1 × 10(6)/unit after leukofiltration. P-Capt prion filtration provided an additional greater than 0.8 log leukoreduction. No serious or unexpected adverse events were observed after infusion of P-Capt-filtered full-volume RBC units. CONCLUSIONS: P-Capt-filtered, stored RBCs demonstrated acceptable viability and no detectable neoantigen expression, immunogenic responses. or safety issues after infusion of a complete unit. The additional filtration time and modest reduction in RBC content are within acceptable levels for implementation in countries with transfusion transmission of vCJD.

Transfusion-related acute lung injury (TRALI): A Canadian blood services research and development symposium.

Since the first description of transfusion-related acute lung injury (TRALI) more than 2 decades ago, we have only recently begun to learn how this disorder may occur and how to prevent it. Scientists from around the world have made great strides in identifying the possible causes of this condition. Blood banks and transfusion services have risen to the challenges of prevention. Recent introduction of restricting most plasma products to those obtained from male donors only has greatly reduced the incidence of TRALI worldwide. Scientists have recently identified the gene and protein for the human neutrophil antigen-3a associated with most mortality due to TRALI, and this presents an opportunity for a screening assay to prevent future TRALI-associated deaths. Finally, animal models of TRALI have provided insight into the possible mechanisms of this disorder and can be used to explore potential treatment modalities.