Results of clinical effectiveness of conventional versus Mirasol-treated Apheresis Platelets in Patients with Hypoproliferative Thrombocytopenia (MiPLATE) trial.

BACKGROUND: The Mirasol® Pathogen Reduction Technology System was developed to reduce transfusion-transmitted diseases in platelet (PLT) products. STUDY DESIGN AND METHODS: MiPLATE trial was a prospective, multicenter, controlled, randomized, non-inferiority (NI) study of the clinical effectiveness of conventional versus Mirasol-treated Apheresis PLTs in participants with hypoproliferative thrombocytopenia. The novel primary endpoint was days of ≥Grade 2 bleeding with an NI margin of 1.6. RESULTS: After 330 participants were randomized, a planned interim analysis of 297 participants (145 MIRASOL, 152 CONTROL) receiving ≥1 study transfusion found a 2.79-relative rate (RR) in the MIRASOL compared to the CONTROL in number of days with ≥Grade 2 bleeding (95% confidence interval [CI] 1.67-4.67). The proportion of subjects with ≥Grade 2 bleeding was 40.0% (n = 58) in MIRASOL and 30.3% (n = 46) in CONTROL (RR = 1.32, 95% CI 0.97-1.81, p = .08). Corrected count increments were lower (p < .01) and the number of PLT transfusion episodes per participant was higher (RR = 1.22, 95% CI 1.05-1.41) in MIRASOL. There was no difference in the days of PLT support (hazard ratio = 0.86, 95% CI 0.68-1.08) or total number of red blood cell transfusions (RR = 1.12, 95% CI 0.91-1.37) between MIRASOL versus CONTROL. Transfusion emergent adverse events were reported in 119 MIRASOL participants (84.4%) compared to 133 (82.6%) participants in CONTROL (p = NS). DISCUSSION: This study did not support that MIRASOL was non-inferior compared to conventional platelets using the novel endpoint number of days with ≥Grade 2 bleeding in MIRASOL when compared to CONTROL.

Reevaluation of the medical necessity of washed red blood cell transfusion in chronically transfused adults.

BACKGROUND: Washing red blood cell (RBC) units mitigates severe allergic transfusion reactions. However, washing reduces the time to expiration and the effective dose. Automated washing is time- and labor-intensive. A shortage of cell processor tubing sets prompted review of medical necessity for washed RBC for patients previously thought to require washing. STUDY DESIGN AND METHODS: A single-center, retrospective study investigated discontinuing wash RBC protocols in chronically transfused adults. In select patients with prior requirements for washing, due to a history of allergic transfusion reactions, trials of unwashed transfusions were performed. Patient demographic, clinical, laboratory, and transfusion data were compiled. The per-unit washing cost was the sum of the tubing set, saline, and technical labor costs. RESULTS: Fifteen patients (median age 34 years interquartile range [IQR] 23-53 years, 46.7% female) were evaluated. These patients had been transfused with a median of 531 washed RBC units (IQR 244-1066) per patient over 12 years (IQR 5-18 years), most commonly for recurrent, non-severe allergic reactions. There were no transfusion reactions with unwashed RBCs aside from one patient with one episode of pruritus and another with recurrent pruritus, which was typical even with washed RBC. We decreased the mean number of washed RBC units per month by 72.9% (104 ± 10 vs. 28.2 ± 25.2; p < .0001) and saved US $100.25 per RBC unit. CONCLUSION: Washing of RBCs may be safely reconsidered in chronically transfused patients without a history of anaphylaxis. Washing should be implemented judiciously due to potential lack of necessity and logistical/operational challenges.

Clinical Outcomes, Blood Utilization, and Ethical Considerations for Pediatric Patients in a Bloodless Medicine and Surgery Program.

BACKGROUND: Pediatric patients requesting bloodless care represent a challenging clinical situation, as parents cannot legally refuse lifesaving or optimal interventions for their children. Here, we report clinical outcomes for the largest series of pediatric inpatients requesting bloodless care and also discuss the ethical considerations. METHODS: We performed a single-institution retrospective cohort study assessing 196 pediatric inpatients (<18 years of age) who requested bloodless care between June 2012 and June 2016. Patient characteristics, transfusion rates, and clinical outcomes were compared between pediatric patients receiving bloodless care and those receiving standard care (including transfusions if considered necessary by the clinical team) (n = 37,271). Families were informed that all available measures would be undertaken to avoid blood transfusions, although we were legally obligated to transfuse blood if the child's life was threatened. The primary outcome was composite morbidity or mortality. Secondary outcomes included percentage of patients transfused, individual morbid events, length of stay, total hospital charges, and total costs. Subgroup analyses were performed after stratification into medical and surgical patients. RESULTS: Of the 196 pediatric patients that requested bloodless care, 6.1% (n = 12) received an allogeneic blood component, compared to 9.1% (n = 3392) for standard care patients ( P = .14). The most common indications for transfusion were perioperative bleeding and anemia of prematurity. None of the transfusions were administered under a court order. Overall, pediatric patients receiving bloodless care exhibited lower rates of composite morbidity compared to patients receiving standard care (2.6% vs 6.2%; P = .035). There were no deaths in the bloodless cohort. Individual morbid events, length of stay, and total hospital charges/costs were not significantly different between the 2 groups. After multivariable analysis, bloodless care was not associated with a significant difference in composite morbidity or mortality (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.12-1.11; P = .077). CONCLUSIONS: Pediatric patients receiving bloodless care exhibited similar clinical outcomes compared to patients receiving standard care, although larger studies with adequate power are needed to confirm this finding. There were no mortalities among the pediatric bloodless cohort. Although a subset of our pediatric bloodless patients received an allogeneic transfusion, no patients required a court order. When delivered in a collaborative and patient-centered manner, blood transfusions can be safely limited among pediatric patients.

De Novo Frameshift Variants in the Neuronal Splicing Factor NOVA2 Result in a Common C-Terminal Extension and Cause a Severe Form of Neurodevelopmental Disorder.

The neuro-oncological ventral antigen 2 (NOVA2) protein is a major factor regulating neuron-specific alternative splicing (AS), previously associated with an acquired neurologic condition, the paraneoplastic opsoclonus-myoclonus ataxia (POMA). We report here six individuals with de novo frameshift variants in NOVA2 affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and abnormal brain MRI. The six variants lead to the same reading frame, adding a common proline rich C-terminal part instead of the last KH RNA binding domain. We detected 41 genes differentially spliced after NOVA2 downregulation in human neural cells. The NOVA2 variant protein shows decreased ability to bind target RNA sequences and to regulate target AS events. It also fails to complement the effect on neurite outgrowth induced by NOVA2 downregulation in vitro and to rescue alterations of retinotectal axonal pathfinding induced by loss of NOVA2 ortholog in zebrafish. Our results suggest a partial loss-of-function mechanism rather than a full heterozygous loss-of-function, although a specific contribution of the novel C-terminal extension cannot be excluded.

Associations between ABO non-identical platelet transfusions and patient outcomes-A multicenter retrospective analysis.

BACKGROUND: Due to platelet availability limitations, platelet units ABO mismatched to recipients are often transfused. However, since platelets express ABO antigens and are collected in plasma which may contain ABO isohemagglutinins, it remains controversial as to whether ABO non-identical platelet transfusions could potentially pose harm and/or have reduced efficacy. STUDY DESIGN AND METHODS: The large 4-year publicly available Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) database was used to investigate patient outcomes associated with ABO non-identical platelet transfusions. Outcomes included mortality, sepsis, and subsequent platelet transfusion requirements. RESULTS: Following adjustment for possible confounding factors, no statistically significant association between ABO non-identical platelet transfusion and increased risk of mortality was observed in the overall cohort of 21,176 recipients. However, when analyzed by diagnostic category and recipient ABO group, associations with increased mortality for major mismatched transfusions were noted in two of eight subpopulations. Hematology/Oncology blood group A and B recipients (but not group O) showed a Hazard Ratio (HR) of 1.29 (95%CI: 1.03-1.62) and intracerebral hemorrhage group O recipients (but not groups A and B) showed a HR of 1.75 (95%CI: 1.10-2.80). Major mismatched transfusions were associated with increased odds of receiving additional platelet transfusion each post-transfusion day (through day 5) regardless of the recipient blood group. DISCUSSION: We suggest that prospective studies are needed to determine if specific patient populations would benefit from receiving ABO identical platelet units. Our findings indicate that ABO-identical platelet products minimize patient exposure to additional platelet doses.

SARS-CoV-2 seroprevalence among blood donors in Uganda: 2019-2022.

BACKGROUND: The true burden of COVID-19 in low- and middle-income countries remains poorly characterized, especially in Africa. Even prior to the availability of SARS-CoV-2 vaccines, countries in Africa had lower numbers of reported COVID-19 related hospitalizations and deaths than other regions globally. METHODS: Ugandan blood donors were evaluated between October 2019 and April 2022 for IgG antibodies to SARS-CoV-2 nucleocapsid (N), spike (S), and five variants of the S protein using multiplexed electrochemiluminescence immunoassays (MesoScale Diagnostics, Rockville, MD). Seropositivity for N and S was assigned using manufacturer-provided cutoffs and trends in seroprevalence were estimated by quarter. Statistically significant associations between N and S antibody seropositivity and donor characteristics in November-December 2021 were assessed by chi-square tests. RESULTS: A total of 5393 blood unit samples from donors were evaluated. N and S seropositivity increased throughout the pandemic to 82.6% in January-April 2022. Among seropositive individuals, N and S antibody levels increased ≥9-fold over the study period. In November-December 2021, seropositivity to N and S antibody was higher among repeat donors (61.3%) compared with new donors (55.1%; p = .043) and among donors from Kampala (capital city of Uganda) compared with rural regions (p = .007). Seropositivity to S antibody was significantly lower among HIV-seropositive individuals (58.8% vs. 84.9%; p = .009). CONCLUSIONS: Despite previously reported low numbers of COVID-19 cases and related deaths in Uganda, high SARS-CoV-2 seroprevalence and increasing antibody levels among blood donors indicated that the country experienced high levels of infection over the course of the pandemic.

U.S. cities will not meet blood product resuscitation standards during major mass casualty incidents: Results of a THOR-AABB working party prospective analysis.

BACKGROUND: Mass casualty incidents (MCIs) create an immediate surge in blood product demand. We hypothesize local inventories in major U.S. cities would not meet this demand. STUDY DESIGN AND METHODS: A simulated blast in a large crowd estimated casualty numbers. Ideal resuscitation was defined as equal amounts of red blood cells (RBCs), plasma, platelets, and cryoprecipitate. Inventory was prospectively collected from six major U.S. cities at six time points between January and July 2019. City-wide blood inventories were classified as READY (>1 U/injured survivor), DEFICIENT (<10 U/severely injured survivor), or RISK (between READY and DEFICIENT), before and after resupply from local distribution centers (DC), and features of DEFICIENT cities were identified. RESULTS: The simulated blast resulted in 2218 injured survivors including 95 with severe injuries. Balanced resuscitation would require between 950 and 2218 units each RBC, plasma, platelets and cryoprecipitate. Inventories in 88 hospitals/health systems and 10 DCs were assessed. Of 36 city-wide surveys, RISK inventories included RBCs (n = 16; 44%), plasma (n = 24; 67%), platelets (n = 6; 17%), and cryoprecipitate (n = 22; 61%) while DEFICIENT inventories included platelets (n = 30; 83%) and cryoprecipitate (n = 12; 33%). Resupply shifted most RBC and plasma inventories to READY, but some platelet and cryoprecipitate inventories remained at RISK (n = 24; 67% and n = 12; 33%, respectively) or even DEFICIENT (n = 11; 31% and n = 6; 17%, respectively). Cities with DEFICIENT inventories were smaller (p <.001) with fewer blood products per trauma bed (p <.001). DISCUSSION: In this simulated blast event, blood product demand exceeded local supply in some major U.S. cities. Options for closing this gap should be explored to optimize resuscitation during MCIs.

Methods of Bloodless Care, Clinical Outcomes, and Costs for Adult Patients Who Decline Allogeneic Transfusions.

BACKGROUND: Providing bloodless medical care for patients who wish to avoid allogeneic transfusion can be challenging; however, previous studies have demonstrated favorable outcomes when appropriate methods are used. Here, we report one of the largest series of patients receiving bloodless care, along with the methods used to provide such care, and the resulting outcomes. METHODS: In a retrospective cohort study, 1111 adult inpatients (age ≥18 years) at a single institution who declined allogeneic transfusion for religious or personal reasons between June 2012 and June 2016 were included, and the patient blood management methods are described. Patient characteristics, laboratory data, and transfusion rates, as well as clinical outcomes (morbidity, mortality, and length of stay) were compared to all other patients in the hospital who received standard care, including transfusions if needed (n = 137,009). Medical and surgical patients were analyzed as subgroups. The primary outcome was composite morbidity (any morbid event: infectious, thrombotic, ischemic, renal, or respiratory). Secondary outcomes included individual morbid events, in-hospital mortality, length of stay, total hospital charges, and costs. RESULTS: The bloodless cohort had more females and a lower case mix index, but more preadmission comorbidities. Mean nadir hemoglobin during hospitalization was lower in the bloodless (9.7 ± 2.6 g/dL) compared to the standard care (10.1 ± 2.4 g/dL) group (P < .0001). Composite morbidity occurred in 14.4% vs 16.0% (P = .16) of the bloodless and standard care patients, respectively. Length of stay and in-hospital mortality were similar between the bloodless and standard care patients. After Bonferroni adjustment for multiple comparisons, hospital-acquired infection occurred less frequently in the bloodless compared to the standard care cohort (4.3% vs 8.3%) (P < .0001) in the medical patient subgroup, but not in the surgical subgroup. After propensity score adjustment in a multivariable model and adjustment for multiple comparisons, bloodless care was associated with less risk of hospital-acquired infection (OR, 0.56; 95% CI, 0.35-0.83; P = .0074) in the medical subgroup, but not in the surgical subgroup. Median total hospital charges (by 8.5%; P = .0017) and costs (by 8.7%; P = .0001) were lower in the bloodless compared to the standard care cohort, when all patients were included. CONCLUSIONS: Overall, adult patients receiving bloodless care had similar clinical outcomes compared to patients receiving standard care. Medical (but not surgical) bloodless patients may be at less risk for hospital-acquired infection compared to those receiving standard care. Bloodless care is cost-effective and should be considered as high-value practice.

Therapeutic plasma exchange for the treatment of refractory necrotizing autoimmune myopathy.

INTRODUCTION: Necrotizing autoimmune myopathy (NAM) is strongly associated with pathognomonic autoantibodies targeting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) or signal recognition particle (SRP), whose levels in turn are correlated with serum creatine kinase (CK) and necrosis. Thus, NAM may be amenable to therapeutic plasma exchange (TPE) to remove pathogenic antibodies and improve patient symptoms. METHODS: A retrospective case series and literature review of patients presenting with NAM and undergoing treatment with TPE was performed. Clinical data including patient demographics, symptoms, physical exam findings, muscle biopsy, lower extremity imaging, prior therapy, and duration from diagnosis to TPE initiation were collected retrospectively for adult patients with NAM treated with TPE after failing to respond to immunomodulatory therapy. Laboratory data including change in CK levels and myositis-specific antibody titers from baseline were measured in some patients. RESULTS: Six patients (median age at diagnosis 52.5 years, interquartile range [IQR] 35.8-64.5 years, four male/two female) underwent a median of 7.5 (IQR: 5-10) TPE procedures with 5% albumin as replacement. All patients exhibited a statistically significant reduction in CK level from pre-TPE baseline (range: 43.0%-58.7% reduction). Responses in this cohort were best in patients with antibodies targeting HMGCR and SRP, which are most strongly associated with NAM. These results compare favorably to a literature review of NAM patients (n = 19) treated with TPE, who also exhibited positive clinical and laboratory responses across varying treatment lengths. CONCLUSION: TPE can play a role in the management of NAM, particularly in patients with HMGCR or SRP antibodies who are refractory to pharmacologic immunosuppression.

Bacterial contamination of blood products in Africa.

BACKGROUND: Bacterial contamination of blood components (notably platelets) remains a leading infectious risk to the blood supply. There has been extensive research in high-income countries to characterize the risk of bacterial contamination along with adoption of strategies to mitigate that risk. By contrast, related data in Africa are lacking. STUDY DESIGN AND METHODS: An electronic survey was distributed to members of African Society of Blood Transfusion to assess existing or planned measures at African blood centers and hospitals to mitigate bacterial contamination of blood products. A literature review of studies pertaining to related transfusion-associated risk in Africa was conducted to complement the findings. RESULTS: Forty-five responses were received, representing 16 African countries. All respondents were urban, either in blood centers (n = 36) or hospital-based transfusion services (n = 9). Reported measures included skin disinfection (n = 41 [91.1%]); diversion pouches (n = 14 [31.1%]); bacterial culture (n = 9 [20%]); pathogen reduction (PR) (n = 3 [6.7%]); and point-of-release testing (PoRT) (n = 2 [4.4%]). Measures being considered for implementation included: skin disinfection (n = 2 [4.4%]); diversion pouches (n = 2 [4.4%]); bacterial culture n = 14 (31.1%); PR (n = 11 [24.4%]); and PoRT (n = 4 [8.9%]). Of the 38 respondents who reported collection of platelets, 14 (36.8%) and 8 (21.1%) reported using diversion pouches and bacterial culture, respectively. The literature review identified 36 studies on the epidemiology of bacterial contamination and septic transfusion reactions in Africa; rates of contamination ranged from 0% to 17.9%. CONCLUSIONS: The findings suggest that prevention of bacterial contamination of blood components and transfusion-associated sepsis in Africa remains neglected. Regional preventive measures have not been widely adopted.

Plasma trial: Pilot randomized clinical trial to determine safety and efficacy of plasma transfusions.

BACKGROUND: Plasma is frequently administered to patients with prolonged INR prior to invasive procedures. However, there is limited evidence evaluating efficacy and safety. STUDY DESIGN AND METHODS: We performed a pilot trial in hospitalized patients with INR between 1.5 and 2.5 undergoing procedures conducted outside the operating room. We excluded patients undergoing procedures proximal to the central nervous system, platelet counts <40,000/µl, or congenital or acquired coagulation disorders unresponsive to plasma. We randomly allocated patients stratified by hospital and history of cirrhosis to receive plasma transfusion (10-15 cc/kg) or no transfusion. The primary outcome was change in hemoglobin concentration within 2 days of procedure. RESULTS: We enrolled 57 patients, mean age 56.0, 34 (59.6%) with cirrhosis, and mean INR 1.92 (SD = 0.27). In the intention to treat analysis, there were 10 of 27 (38.5%) participants in the plasma arm with a post procedure INR <1.5 and one of 30 (3.6%) in the no treatment arm (p < .01). The mean INR after receiving plasma transfusion was -0.24 (SD 0.26) lower than baseline. The change from pre-procedure hemoglobin level to lowest level within 2 days was -0.6 (SD = 1.0) in the plasma transfusion arm and -0.4 (SD = 0.6) in the no transfusion arm (p = .29). Adverse outcomes were uncommon. DISCUSSION: We found no differences in change in hemoglobin concentration in those treated with plasma compared to no treatment. The change in INR was small and corrected to less than 1.5 in minority of patients. Large trials are required to establish if plasma is safe and efficacious.

Blood transfusions in gunshot-wound-related emergency department visits and hospitalizations in the United States.

BACKGROUND: The United States (US) leads all high-income countries in gunshot wound (GSW) deaths. However, previous US studies have not evaluated the national blood transfusion utilization patterns in hospitalized GSW patients. METHODS: Data from 2016 to 2017 were analyzed from the Nationwide Emergency Department Sample (NEDS) and Nationwide Inpatient Sample (NIS), the largest all-payer emergency department (ED) and inpatient databases, respectively. Using stratified probability sampling, weights were applied to generate nationally representative estimates. Multivariable Poisson-regression models were used to estimate prevalence ratios (PR) of blood transfusion. RESULTS: There were 168,315 ED visits and 58,815 hospitalizations (age = 18-90 years) following a GSW. The majority of hospitalizations were men (88.5%), age 18-24 years (31.8%), and assault-related GSW (51.3%). Blacks had the largest proportion (48.7%) overall of all GSW hospitalizations; Whites accounted for the highest proportion of intentional self-harm injuries (72.4%). Blood transfusions occurred in 12.7% of hospitalizations (12.0% red blood cell [RBC], 4.9% plasma, and 2.5% platelet transfusions). Only 1.9% of cases were associated with transfusion of all three blood components. Hospitalizations with major/extreme severity of illness had significantly higher prevalence of transfusion versus those with mild/moderate severity [crude PR = 4.79 (95%CI:4.15-5.33, p < .001)]. Overall, 8.2% of hospitalizations with GSW died, of whom 26.8% required blood transfusions, which was significantly higher than survivors [crude PR = 2.34 (95%CI:2.10-2.61, p < .001)]. The vast majority (95%) of the transfusions among those who died were within 48 h since admission. CONCLUSIONS: Gun-related violence is a public health emergency in the US, and GSWs are a source of significant mortality, blood utilization, and health care costs.

Civilian walking blood bank emergency preparedness plan.

BACKGROUND: The current global pandemic has created unprecedented challenges in the blood supply network. Given the recent shortages, there must be a civilian plan for massively bleeding patients when there are no blood products on the shelf. Recognizing that the time to death in bleeding patients is less than 2 h, timely resupply from unaffected locations is not possible. One solution is to transfuse emergency untested whole blood (EUWB), similar to the extensive military experience fine-tuned over the last 19 years. While this concept is anathema in current civilian transfusion practice, it seems prudent to have a vetted plan in place. METHODS AND MATERIALS: During the early stages of the 2020 global pandemic, a multidisciplinary and international group of clinicians with broad experience in transfusion medicine communicated routinely. The result is a planning document that provides both background information and a high-level guide on how to emergently deliver EUWB for patients who would otherwise die of hemorrhage. RESULTS AND CONCLUSIONS: Similar plans have been utilized in remote locations, both on the battlefield and in civilian practice. The proposed recommendations are designed to provide high-level guidance for experienced blood bankers, transfusion experts, clinicians, and health authorities. Like with all emergency preparedness, it is always better to have a well-thought-out and trained plan in place, rather than trying to develop a hasty plan in the midst of a disaster. We need to prevent the potential for empty shelves and bleeding patients dying for lack of blood.

Home video prediction of epileptic vs. nonepileptic seizures in US veterans.

OBJECTIVE: Using video-EEG (v-EEG) diagnosis as a gold standard, we assessed the predictive diagnostic value of home videos of spells with or without additional limited demographic data in US veterans referred for evaluation of epilepsy. Veterans, in particular, stand to benefit from improved diagnostic tools given higher rates of PNES and limited accessibility to care. METHODS: This was a prospective, blinded diagnostic accuracy study in adults conducted at the Houston VA Medical Center from 12/2015-06/2019. Patients with a definitive diagnosis of epileptic seizures (ES), psychogenic nonepileptic seizures (PNES), or physiologic nonepileptic events (PhysNEE) from v-EEG monitoring were asked to submit home videos. Four board-certified epileptologists blinded to the original diagnosis formulated a diagnostic impression based upon the home video review alone and video plus limited demographic data. RESULTS: Fifty patients (30 males; mean age 47.7 years) submitted home videos. Of these, 14 had ES, 33 had PNES, and three had PhysNEE diagnosed by v-EEG. The diagnostic accuracy by video alone was 88.0%, with a sensitivity of 83.9% and specificity of 89.6%. Providing raters with basic patient demographic information in addition to the home videos did not significantly improve diagnostic accuracy when comparing to reviewing the videos alone. Inter-rater agreement between four raters based on video was moderate with both videos alone (kappa = 0.59) and video plus limited demographic data (kappa = 0.60). SIGNIFICANCE: This study demonstrated that home videos of paroxysmal events could be an important tool in reliably diagnosing ES vs. PNES in veterans referred for evaluation of epilepsy when interpreted by experts. A moderate inter-rater reliability was observed in this study.

How do you decide which platelet bacterial risk mitigation strategy to select for your hospital-based transfusion service?

The United States Food and Drug Administration Final Guidance for Industry titled, "Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion" provides nine strategies for platelet bacterial risk mitigation. Even if it is assumed all strategies are comparable in terms of safety and efficacy, the decision of which to implement remains challenging. Some additional factors that warrant evaluation before selecting a strategy include the financial impact, process for implementation, logistics upon implementation, institutional acceptance by blood bank staff, administration and clinicians, and effect on platelet availability. To assist with this difficult choice, a panel of transfusion service physicians who have expertise on the topic and have already selected strategies for their transfusion services were recruited to provide varied perspectives. In addition, the use of a decision-making tool that objectively evaluates defined criteria for assessment of the nine strategies is described.

Financial analysis of large-volume delayed sampling to reduce bacterial contamination of platelets.

BACKGROUND: Effective and financially viable mitigation approaches are needed to reduce bacterial contamination of platelets in the US. Expected costs of large-volume delayed sampling (LVDS), which would be performed by a blood center prior to shipment to a hospital, were compared to those of pathogen reduction (PR), point-of-release testing (PORt), and secondary bacterial culture (SBC). METHODS: Using a Markov-based decision-tree model, the financial and clinical impact of implementing all variants of LVDS, PR, PORt, and SBC described in FDA guidance were evaluated from a hospital perspective. Hospitals were assumed to acquire leukoreduced apheresis platelets, with LVDS adding $30 per unit. Monte Carlo simulations were run to estimate the direct medical costs for platelet acquisition, testing, transfusion, and possible complications associated with each approach. Input parameters, including test sensitivity and specificity, were drawn from existing literature and costs (2018US$) were based on a hospital perspective. A one-way sensitivity analysis varied the assumed additional cost of LVDS. RESULTS: Under an approach of LVDS (7-day), the total cost per transfused unit is $735.78, which falls between estimates for SBC (7-day) and PORt. Assuming 20,000 transfusions each year, LVDS would cost $14.72 million annually. Per-unit LVDS costs would need to be less than $22.32 to be cheaper per transfusion than all other strategies, less than $32.02 to be cheaper than SBC (7-day), and less than $196.19 to be cheaper than PR (5-day). CONCLUSIONS: LVDS is an effective and cost-competitive approach, assuming additional costs to blood centers and associated charges to hospitals are modest.

The epidemiology of platelet transfusions: an analysis of platelet use at 12 US hospitals.

BACKGROUND: Using the Recipient and Donor Epidemiology Study-III (REDS-III) recipient and donor databases, we performed a retrospective analysis of platelet use in 12 US hospitals that were participants in REDS-III. STUDY DESIGN AND METHODS: Data were electronically extracted from participating transfusion service and blood center computer systems and from medical records of the 12 REDS-III hospitals. All platelet transfusions from 2013 to 2016 given to patients aged 18 years and older were included in the analysis. RESULTS: There were 28,843 inpatients and 2987 outpatients who were transfused with 163,719 platelet products (103,371 apheresis, 60,348 whole blood derived); 93.5% of platelets were leukoreduced and 72.5% were irradiated. Forty-six percent were transfused to patients with an International Classification of Diseases, 9th/10th Revision (ICD-9/10) diagnosis of leukemia, myelodysplastic syndrome (MDS), or lymphoma. The general ward and the intensive care unit (ICU) were the most common issue locations. Only 54% of platelet transfusions were ABO identical; and 60.6% of platelet transfusions given to Rh-negative patients were Rh positive. The most common pretransfusion platelet count range for inpatients was 20,000 to 50,000/µL, for outpatients it was 10,000 to 20,000/µL. Among ICU patients, 35% of platelet transfusion episodes had a platelet count of greater than 50,000/µL; this was only 8% for general ward and 2% for outpatients. The median posttransfusion increment, not corrected for platelet dose and/or patient size, ranged from 12,000 to 20,000/µL for inpatients, and from 17,000 to 27,000/µL for outpatients. CONCLUSIONS: These data from one of the largest reviews of platelet transfusion practice to date provide guidance for where to focus future clinical research studies and platelet blood management programs.

Solvent detergent treated pooled plasma and reduction of allergic transfusion reactions.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) patients have increased risk for allergic transfusion reactions (ATR) due to the number of plasma products they require. This study evaluated the efficacy of solvent detergent treated plasma (S/D treated plasma) to reduce ATRs. STUDY DESIGN AND METHODS: All TTP patients who presented from April 2014 to February 2015 and experienced a moderate-severe ATR to untreated plasma with TPE were switched to S/D treated plasma (Octaplas) for their remaining procedures and included in the study. Patient records were retrospectively reviewed. RESULTS: The overall ATR rate per procedure decreased from 35.0% (95% CI = 15.4%-59.2%) with untreated plasma to 1.4% ([1/73] 95% CI = 0.0%-7.4%) with S/D treated plasma. The moderate-severe ATR rate decreased from 20.0% ([4/20] 95% CI = 5.7%-43.7%) with untreated plasma to 0.0% ([0/73] 95% CI = 0.0%-4.9%) with S/D treated plasma. The overall ATR rate per plasma unit decreased from 2.6% (95%CI = 1.0%-5.1%) with untreated plasma to 0.1% (95% CI = 0.0%-0.4%) with S/D treated plasma. No patients experienced VTE while receiving untreated plasma. Four patients experienced VTE events while receiving S/D treated plasma. All patients who experienced a VTE had additional risk factors for VTE. CONCLUSION: S/D plasma has promise as an effective product to reduce the risk of ATRs in TTP patients. Given the high risk of ATR in TTP patients, consideration of S/D plasma instead of untreated plasma for TPE in these patients may be warranted, especially for patients with a history of moderate to severe ATR. More extensive studies are needed to confirm these findings.

Secondary bacterial culture of platelets to mitigate transfusion-associated sepsis: A 3-year analysis at a large academic institution.

BACKGROUND: In 2019, the United States Food and Drug Administration published its final recommendations to mitigate bacterial contamination of platelets. We sought to evaluate our secondary bacterial culture (SBC) strategy in light of those recommendations. STUDY DESIGN AND METHODS: A retrospective analysis was conducted of SBC data (October 2016-2019) at our institution. SBC was performed upon receipt (Day 3 after collection); 5 mL of platelet product was inoculated aseptically into an aerobic bottle and incubated at 35°C for 3 days. For 8 months, a 10-mL inoculum was trialed. No quarantine was applied. All positive cultures underwent Gram staining and repeat culture of the platelet product (if available). A probable true positive was defined as concordant positive culture between the initial and repeat culture. The incidence of probable true- and false-positive cultures were reported descriptively and differences evaluated by sampling volume. RESULTS: Over 3 years, 55 896 platelet products underwent SBC, yielding 30 initial positive results (approx. 1/1863 platelets); 25 (83.3%) signaled within 24 hours of SBC. The rates of probable true positive, false positive, and indeterminate for 5 mL were 0.027% (1/3771), 0.002% (1/45 251) and 0.018% (1/5656), respectively. The respective rates for 10 mL were 0.018% (1/5323), 0.07% (1/1521), and 0%. Seven of eight (87.5%) false-positive SBCs occurred with a 10-mL inoculum. No septic transfusion reactions were reported. CONCLUSION: SBC continues to interdict bacterially contaminated units of platelets. Our findings suggest higher rates of false positivity using large-volume inocula.

Comparative changes of pre-operative autologous transfusions and peri-operative cell salvage in the United States.

BACKGROUND: With improved safety of allogeneic blood supply, the use of preoperative autologous donations (PADs) and perioperative autologous cell salvage (PACS) has evolved. This study evaluated temporal trends in PAD and PACS use in the United States. METHODS: The National Inpatient Sample database, a stratified probability sample of 20% of hospitalizations in the United States, was used to compare temporal trends in hospitalizations reporting use of PADs and PACS from 1995 to 2015. Factors associated with their use were examined between 2012 and 2015 with use of multivariable Poisson regression. Sampling weights were applied to generate nationally representative estimates. RESULTS: There was a steady decrease in hospitalizations reporting PAD transfusions from 27.90 per 100 000 in 1995 to 1.48 per 100 000 hospitalizations in 2015 (P-trend <.001). In contrast, PACS increased from a rate of 1.16 per 100 000 in 1995 to peak of 20.51 per 100 000 hospitalizations in 2008 and then steadily declined (P-trend<.001). Higher odds of PACS and PADs were observed in older patients, elective procedures (vs urgent), and urban teaching/nonteaching hospitals (vs rural hospitals) (P < .001). PACS was more common in hospitalizations in patients with higher levels of severity of illness as compared to those with minor severity (adjusted prevalence ratio [adjPR], 2.39; 95% confidence interval [CI], 2.08-2.73; P<.001), while PADs were performed less often in patients with higher underlying severity of illness (All Patient Refined Diagnosis Related Groups, 4 vs 1, adjPR, 0.61; 95% CI, [0.39-0.95]; P = .028). CONCLUSIONS: There was a significant decrease in PAD red blood cell transfusions, while PACS has increased and subsequently decreased; PACS plays an important role in surgical blood conservation. The subsequent decline in PACS likely reflects further optimization of transfusion practice through patient blood management programs and improvement of surgical interventions.