Search

Units of red blood cell (RBC) concentrates with rare phenotypes are typically not included in method validation studies for cryopreservation processes; rather, they are reserved for patients with rare blood needs. Some rare RBC phenotypes may demonstrate membrane abnormalities, like acanthocytosis as observed for RBCs with the McLeod phenotype, and are specifically banked for these rare attributes; however, the impact that rare RBC phenotypes have on post-thaw quality has not been well studied. To evaluate how a rare RBC phenotype is affected by the cryopreservation process, 4 RBC units, cryopreserved in 1993 using manual methods, were selected for evaluation. These RBCs included one with the McLeod phenotype and three with phenotypes not known to cause significant membrane changes. Post-thaw, an altered deglycerolization protocol, implemented to reduce supernatant glycerol after cryopreservation, was used before processing RBCs on an automated closed system (ACP 215; Haemonetics, Boston, MA) to accommodate the use of a closed system cell processor not available when the RBC units were previously cryopreserved. RBC quality was tested at 24 hours, 7 days, and 14 days post-deglycerolization. Before deglycerolization, an extracted sample from the thawed glycerolized RBC unit was used to obtain genetic material for phenotype confirmation. Genotyping confirmed the McLeod phenotype. When comparing McLeod with non-McLeod units, RBCs from the McLeod donor exhibited acanthocytosis, higher rigidity, and lower morphology scores than RBCs from the non-McLeod units post-deglycerolization. Hemolysis, however, was comparable across all 4 units, meeting regulatory standards. Therefore, McLeod RBCs can withstand cryopreservation, suggesting that units from these donors, glycerolized using older methods, can be deglycerolized using the ACP 215 and stored hypothermically for 14 days. It was also determined that genotyping can be performed on non-leukocyte-reduced cryopreserved RBCs, allowing for confirmation of genetic profiles of donor units banked before the implementation of molecular methods. Units of red blood cell (RBC) concentrates with rare phenotypes are typically not included in method validation studies for cryopreservation processes; rather, they are reserved for patients with rare blood needs. Some rare RBC phenotypes may demonstrate membrane abnormalities, like acanthocytosis as observed for RBCs with the McLeod phenotype, and are specifically banked for these rare attributes; however, the impact that rare RBC phenotypes have on post-thaw quality has not been well studied. To evaluate how a rare RBC phenotype is affected by the cryopreservation process, 4 RBC units, cryopreserved in 1993 using manual methods, were selected for evaluation. These RBCs included one with the McLeod phenotype and three with phenotypes not known to cause significant membrane changes. Post-thaw, an altered deglycerolization protocol, implemented to reduce supernatant glycerol after cryopreservation, was used before processing RBCs on an automated closed system (ACP 215; Haemonetics, Boston, MA) to accommodate the use of a closed system cell processor not available when the RBC units were previously cryopreserved. RBC quality was tested at 24 hours, 7 days, and 14 days post-deglycerolization. Before deglycerolization, an extracted sample from the thawed glycerolized RBC unit was used to obtain genetic material for phenotype confirmation. Genotyping confirmed the McLeod phenotype. When comparing McLeod with non-McLeod units, RBCs from the McLeod donor exhibited acanthocytosis, higher rigidity, and lower morphology scores than RBCs from the non-McLeod units post-deglycerolization. Hemolysis, however, was comparable across all 4 units, meeting regulatory standards. Therefore, McLeod RBCs can withstand cryopreservation, suggesting that units from these donors, glycerolized using older methods, can be deglycerolized using the ACP 215 and stored hypothermically for 14 days. It was also determined that genotyping can be performed on non-leukocyte–reduced cryopreserved RBCs, allowing for confirmation of genetic profiles of donor units banked before the implementation of molecular methods.

Plasma is often transfused to patients with bleeding or requiring invasive procedures and with abnormal tests of coagulation. Chart audits find half of plasma transfusions unnecessary, resulting in avoidable complications and costs. This multicentre electronic audit was conducted to determine the proportion of plasma transfused without an indication and/or at a sub-therapeutic dose.Data were extracted on adult inpatients in 2017 at five academic sites from the hospital electronic chart, laboratory information systems and the Canadian Institute for Health Information Discharge Abstract Database. Electronic criteria for plasma transfusion outside recommended indications were: (1) international normalized ratio (INR) 1.5 with no to moderate bleeding; (2) INR ≥ 1.5, with no to mild bleeding and no planned procedures; and (3) no INR before or after plasma infusion. Sub-therapeutic dose was defined as ≤2 units transfused.In 1 year, 2590 patients received 6088 plasma transfusions encompassing 11,490 units of plasma occurred at the five sites. 77.7% of events were either outside indications or under-dosed. Of these, 34.8% of plasma orders had no indication identified, and 62% of these occurred in non-bleeding patients and no planned procedure with an isolated elevated INR. 70.7% of transfusions were under-dosed. Most plasma transfusions occurred in the intensive care unit or the operating room. Inter-hospital variability in peri-transfusion testing and dosing was observed.The majority of plasma transfusions are sub-optimal. Local hospital culture may be an important driver. Electronic audits, with definitions employed in this study, may be a practical alternative to costly chart audits.

Background West Nile Virus (WNV) is a member of the Japanese Encephalitis (JE) serocomplex within the Flaviviridae family. We report four whole blood donors and one plasma donor with WNV nucleic acid test (NAT)-reactive donations between September 2018 and November 2019, following recent Japanese Encephalitis virus (JEV) vaccination. Case series Cases 1 and 4 had reactive WNV NAT donations 1 day after receiving the JEV vaccine. Case 2 had a reactive WNV donation 3 days after receiving the JEV vaccine. Case 3 had a reactive WNV NAT donation 3 days after returning from Arizona and 1 day after receiving the JEV vaccine. Case 5 had a reactive WNV donation the same day as receiving the JEV vaccine. Study design and methods WNV screening used the Roche cobas WNV nucleic acid test (NAT) (Roche Molecular Systems). Reference testing on WNV-reactive donations was carried out by the National Microbiology Laboratory (NML). JEV vaccine dilutions were also analyzed. Results Supplemental NAT was negative for WNV and JEV for Cases 1, 3, and 5. Case 2 had a weak amplification curve for one of two JEV NAT targets. Case 4 was JEV NAT-positive, WNV NAT-negative. Serologic testing on donation specimens for Cases 2, 4, and 5 did not support recent or remote WNV infection. JEV vaccine dilutions were detected by both cobas and supplemental NAT. Conclusions We recommend implementing a temporary blood donor deferral following a JEV vaccination, if screening utilizes a WNV assay with the capability of detecting other members of the JE serocomplex.

Background Vancomycin-resistant enterococci (VRE) are antibiotic-resistant organisms associated with both colonization and serious life-threatening infection in health care settings. Contamination of platelet concentrates (PCs) with Enterococcus can result in transfusion-transmitted infection. Case presentation This report describes the investigation of a septic transfusion case involving a 27-year-old male patient with relapsed acute leukemia who was transfused with a 5-day-old buffy coat PC pool and developed fever and rigors. Discussion Microbiology testing and pulse-field gel electrophoresis (PFGE) was done on patient blood cultures obtained from peripheral and central lines. Microbiology and molecular testing were also performed on the remaining posttransfusion PC pool, which was refrigerated for 24 hours before microbiology testing. Red blood cell (RBC) and plasma units associated with the implicated PCs were screened for microbial contamination. Patient blood cultures obtained from peripheral and central lines yielded vancomycin-resistant Enterococcus faecium. Gram stain of a sample from the platelet pool was negative but coagulase-negative Staphylococcus (CNST) and VRE were isolated on culture. Antibiotic sensitivity and PFGE profiles of several VRE isolates from the patient before and after transfusion, and the PC pool, revealed that all were closely related. Associated RBC and plasma components tested negative for microbial contamination. Conclusions Microbiological and molecular investigations showed a relationship between VRE isolated from the patient before and after transfusion, and therefore it is postulated that a patient-to-PC retrograde contamination (from either blood or skin) occurred. As the CNST isolated from the PC pool was not isolated from patient samples, its implication in the transfusion event is unknown.

BACKGROUND Contamination of platelet concentrates (PCs) with Staphylococcus aureus is one of the most significant ongoing transfusion safety risks in developed countries. CASE REPORT This report describes a transfusion reaction in an elderly patient diagnosed with acute myeloid leukemia, transfused with a 4-day-old buffy coat PC through a central venous catheter. The transfusion was interrupted when a large fibrous clot in the PC obstructed infusion pump flow. Shortly afterward, a red blood cell (RBC) unit transfusion started. After septic symptoms were developed, the RBC transfusion was also interrupted. While the RBC unit tested negative for bacterial contamination, the PC and the patient samples were found to be contaminated with a S. aureus strain that exhibited the same phenotypic and genome sequencing profiles. The isolated S. aureus forms biofilms and produces the superantigen enterotoxin-like U, which was detected in a sample of the transfused PCs. The patient received posttransfusion antibiotic treatment and had her original central line removed and replaced. DISCUSSION As the implicated PC had been tested for bacterial contamination during routine screening yielding negative results, this is a false-negative transfusion sepsis case. Using a point-of-care test could have prevented the transfusion reaction. This report highlights the increasing incidence of S. aureus as a major PC contaminant with grave clinical implications. Importantly, S. aureus is able to interact with platelet components resulting in visible changes in PCs. CONCLUSION Visual inspection of blood components before transfusion is an essential safety practice to interdict the transfusion of bacterially contaminated units.

BACKGROUND Cryopreserved red blood cell concentrates (RCCs) are often required for patients with rare blood groups. Although transfusions from blood relatives are irradiated before transfusion, research has yet to make clear if this is necessary in cryopreserved RCCs. Given insufficient evidence to the contrary, irradiation of cryopreserved RCCs has been recommended, but the effect of irradiation timing is unknown. Therefore, this study was performed to assess the effect of RCC irradiation pre- and postcryopreservation on RCC quality. STUDY DESIGN AND METHODS Nine whole blood units from healthy donors were processed into RCCs using the buffy coat method. ABO- and Rh-matched units were pooled and split into three groups: precryopreservation irradiation (pre-CIG), postcryopreservation irradiation (post-CIG), and nonirradiated controls. Hemoglobin, hematocrit, white blood cell (WBC) count, extracellular potassium, mean cell volume, red blood cell (RBC) morphology, and RBC deformability were measured. RESULTS Extracellular potassium was greater in the irradiated conditions when compared to the nonirradiated controls and was greater in the post-CIG group when compared to the pre-CIG group (p

Background A massive hemorrhage protocol (MHP) enables rapid delivery of blood components in a patient who is exsanguinating pending definitive hemorrhage control, but there is variability in MHP implementation rates, content and compliance owing to challenges presented by infrequent activation, variable team performance and patient acuity. The goal of this project was to identify the key evidence-based principles and quality indicators required to develop a standardized regional MHP. Methods A modified Delphi consensus technique was performed in the spring and summer of 2018. Panellists used survey links to independently review and rate (on a 7-point Likert scale) 43 statements and 8 quality indicators drafted by a steering committee composed of transfusion medicine specialists and technologists, and trauma physicians. External stakeholder input from all hospitals in Ontario was sought. Results Three rounds were held with 36 experts from diverse clinical backgrounds. Consensus was reached for 42 statements and 8 quality indicators. Additional modifications from external stakeholders were incorporated to form the foundation for the proposed MHP. Interpretation This MHP template will provide the basis for the design of an MHP toolkit, including specific recommendations for pediatric and obstetrical patients, and for hospitals with limited availability of blood components or means to achieve definitive hemorrhage control. We believe that harmonization of MHPs in our region will simplify training, increase uptake of evidence-based interventions, enhance communication, improve patient comfort and safety, and, ultimately, improve patient outcomes.

BACKGROUND The optimal method of providing transfusion medicine (TM) education has not been determined. Transfusion Camp was established in 2012 at the University of Toronto as a centrally delivered TM education program for postgraduate trainees. The impact of Transfusion Camp on knowledge, attitudes, and self-reported behavior was evaluated. METHODS Didactic lectures (delivered locally, by webinar, or recorded) and locally facilitated team-based learning seminars were delivered over 5 days during the academic year to 8 sites: 7 in Canada and 1 in the United Kingdom. Knowledge assessment using a validated 20-question multiple-choice exam was conducted before and after Transfusion Camp. Attitudes and self-reported behavior were collected through a survey. RESULTS Over 2 academic years (July 2016 to June 2018), 390 trainees from 16 different specialties (predominantly anesthesia, 41%; hematology, 14%; and critical care, 7%) attended at least 1 day of Transfusion Camp. The mean pretest score was 10.3 of 20 (±2.9; n = 286) compared with posttest score of 13.0 (±2.8; n = 194; p < 0.0001). Lower pretest score and greater attendance (4-5 days compared with 1-3 days) were associated with larger improvement in posttest score; delivery format, specialty, and postgraduate year were not. Trainees reported an improvement in self-rated abilities to manage TM scenarios; 95% rated TM knowledge as very or extremely important in providing patient care; and 81% indicated that they had applied learning from Transfusion Camp into clinical practice. CONCLUSIONS Transfusion Camp increased TM knowledge, fostered a positive attitude toward TM, and enabled a self-reported positive impact on transfusion practice in postgraduate trainees. It is a novel and scalable approach to delivering TM education.

Transfusion medicine training in Canada is currently undergoing a transformation from a time- and process-based curriculum to a competency-based medical education framework. Transfusion medicine is the first accredited postgraduate medical education training program in Canada to adopt a purely competency-based curriculum. It is serving as an example for a number of other postgraduate medical training programs undergoing a similar transition. The purpose of this review is to highlight the elements of competency-based medical education, describe its application to transfusion medicine training, and report on the development and implementation of the new transfusion medicine curriculum in Canada.

Background Transfusion-associated circulatory overload (TACO) is a leading cause of transfusion-attributable morbidity. It is unclear whether diuretics are safe and effective in preventing this reaction. Materials and methods In a pilot controlled feasibility trial, inpatients 65 years or older ordered a single unit of red blood cells were randomized to pre-transfusion furosemide 20 mg or placebo intravenously. Primary outcome was the ability to enroll 80 patients within a 2-month time period. Secondary feasibility outcomes included proportion of RBC transfusions meeting eligibility criteria, proportion of eligible patients enrolled, and compliance to study protocol. Clinical outcomes included the incidence of TACO and associated complications. Results Nine months of enrollment were required for 80 patients to complete the study, due primarily to fewer transfusions than expected meeting eligibility criteria and lower than anticipated consent rates. Protocol compliance was below target due to missing chart documentation of patient fluid balance, and transfusion infusion time. Blinding was maintained throughout the study and treatment arms were well-balanced. A single case of TACO occurred in each arm, for an overall incidence of 2.5%. No differences in peri-transfusion vital signs, B-natriuretic peptide, or signs of furosemide toxicity were observed. Conclusion The study protocol was not feasible as designed, primarily due to challenges in patient enrollment. Modifications to trial design to improve feasibility in future studies have been identified.

Transfusion-associated circulatory overload (TACO) is a leading cause of serious reactions. In regard to TACO, little is known regarding biomarkers as a predictor, their most informative timing, or thresholds of significance or differentiation from other reactions.In this study of inpatients at risk for TACO (age ≥ 50 years) receiving 1 red blood cell unit, cardiac biomarkers, brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), and high-sensitivity troponin were measured at baseline, 6 to 12 hours (except troponin) posttransfusion, and 18 to 24 hours posttransfusion. Primary outcome was a critical increase in biomarkers (1.5-fold increase and supranormal) at 18 to 24 hours.Fifty-one patients were analyzed; 29% had cardiovascular disease, 73% had one or more cardiac risk factors, and 50% took cardiac or antihypertensive therapies. Although eight (16%) developed an increase in systolic pressure of at least 30 mmHg and four (8%) reported dyspnea and/or cough, none had TACO. At baseline, BNP level was more than 100 ng/L in 59% and NT-proBNP was more than 300 pg/mL in 83%. A total of 25% had a BNP critical increase, 33% had a NT-proBNP critical increase, and 2% had a troponin critical increase at 18 to 24 hours. Overall, 38% had at least one biomarker critical increase and NT-proBNP/BNP concordance was 84%. An increase in the NT-proBNP (1.5-fold increase and300 pg/mL) at 18 to 24 hours was the commonest biomarker change.An increase of the NT-proBNP at 18 to 24 hours may be the preferred surrogate marker for identifying a patient experiencing physiologic difficulty in handling the volume challenge. Larger studies are needed to clarify the risk of TACO for a given pretransfusion biomarker profile and the correlation between TACO and increase in biomarkers after transfusion.

Background: The cornerstone of a massive hemorrhage protocol (MHP) is the rapid delivery of blood components to mitigate the consequences of hemorrhagic shock, coagulopathy, and hypothermia in the exsanguinating patient pending definitive hemorrhage control. MHPs are used to facilitate protocol activation/termination, mobilize an interdisciplinary team, provide immediate access to blood, prioritize rapid blood testing, and commence hypothermia-prevention strategies. Non-randomized, before-after implementation studies have found an association between MHPs and improved patient outcomes, including mortality. There is variability in MHP implementation rates, content, and protocol compliance due to challenges presented by infrequent activation, variable team performance, and patient acuity. Methods: We used a modified Delphi technique to establish the framework for a standardized Provincial MHP toolkit and develop quality indicators. We assembled a panel of 36 content experts to represent relevant stakeholders at 150 Ontario hospitals. Panelists included physicians, nurses, and technologists from anesthesia, trauma, obstetrics, hematology, transfusion, emergency, transport, critical care, as well as representation by blood suppliers and patients. The group represented the diverse geographic healthcare program including academic, pediatric, suburban, and small rural hospitals. Panelists were required to attend a two-day MHP forum and complete all rounds of the Delphi. Panelists used digital surveys (LimeSurvey, Hamburg, Germany) to independently review 43 statements and 8 quality indicators drafted by a steering committee. Each statement was rated on a 7-point Likert scale from "definitely should not" to "definitely should include". Disposition of items was based on critieria determined a priori on the median Likert score. Round 1: (1) score at least >5.5 incorporated as written, (2) 2.6-5.4, discussed at the forum with all panelists, with a 2nd round revision, (3) 5.5, accepted, (2) 2.4-5.4, rewritten and sent for round 3, (3) Results: After 3 rounds, consensus was reached for 42 statements and 8 quality indicators. A 100% response rate was achieved from panelists in all three rounds. There were four main areas that required additional rounds and major modifications: (1) selection of the name of the protocol; (2) selection of the laboratory resuscitation targets; (3) determination of the pack configurations; and, (4) clarification of the role of rVIIa. The obstacle to selecting a unified name for the protocol was that many of the hospitals already had longstanding MHPs with specific names. Consensus on the laboratory targets and pack configuration was achieved by splitting statements into sub-sections. The rVIIa statement required three rounds of review to ensure the phrasing satisfied all the panelists for this controversial therapy. Interpretation: We believe that harmonization of MHPs in our region will simplify training, increase uptake of evidence-based interventions, enhance communication, improve patient safety, and ultimately improve outcomes. We highlight areas that need additional study: (1) RCTs are needed to determine if MHPs improve patient outcomes. (2) A "streamlined" version for community hospitals for stabilization before transfer to a tertiary care centre must be tested. (3) Activation and termination criteria have not been validated. (4) The frequency and type of laboratory testing has not been investigated. (5) Laboratory targets for resuscitation must be tested. (6) Does maintaining normothermia decrease transfusion? (7) Can fibrinogen concentrates and PCCs can be considered equivalent to cryoprecipitate and plasma, respectively? (8) Does compliance with the selected quality indicators result in improved outcome? These MHP recommendations will provide the basis for the design of local MHPs including specific recommendations for pediatric patients and for hospitals where definitive hemorrhage control may not be available. Disclosures Arnold: Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding; Rigel: Consultancy, Research Funding; Principia: Consultancy. Pai:Novartis: Honoraria. Sholzberg:Takeda: Honoraria, Research Funding; Baxalta: Honoraria, Research Funding; Baxter: Honoraria, Research Funding. Zeller:Canadian Blood Services: Consultancy; Pfizer: Other: Advisory Board; Ontario Ministry of Health and Long Term Care: Consultancy. Pavenski:Ablynx: Honoraria, Research Funding; Bioverativ: Research Funding; Shire: Honoraria; Alexion: Honoraria, Research Funding; Octapharma: Research Funding.

Importance: Plasma is frequently transfused to patients who are bleeding or require an invasive procedure and have a deficiency of coagulation factors. Despite published guidelines delineating optimal plasma use, two recent audits have suggested that over 50% of the plasma transfused is unnecessary. Inappropriate utilization of plasma has numerous adverse consequences for the recipient, as well as the health care system. Objective: To determine the proportion of inappropriate plasma use with a multicenter electronic data audit and identify focused areas for intervention to reduce inappropriate use. Setting: 3 tertiary care academic sites across Ontario, Canada: Hamilton Health Sciences Centre (Hamilton, Ontario), Sunnybrook Health Sciences Centre (Toronto, Ontario), London Health Sciences Centre (London, Ontario). Participants: All adult inpatients receiving plasma during the time period January 1, 2017 and December 31, 2017. Design: Four areas of inappropriate plasma use in adult patients were defined: (1) patients with a normal INR 1.5, without active bleeding or procedures in 6 hours after plasma transfusion (1 calendar day when time of procedure was not available); (3) no INR drawn before or after plasma infusion; (4) inappropriate non-therapeutic plasma dose of plasma (≤ 2 units) . Results: A total 4,385 plasma transfusion events occurred in 1,844 inpatient admissions. Appropriate indication and dosing was found in 813 (18.5%) of the events. Inappropriate compliance occurred in 3,572 (81.5%) of the events: 608 (13.9%) events occurred in the pre-specified criteria (1-3) above; inappropriate dosing alone occurred in 1,583 (36.1%) events; and, a combination of inappropriate dosing in addition to any 1-3 pre-defined categories occurred in 1,381 (31.5%) transfusion events. Patients transfused with a documented INR (81.5%) in the 24 hours preceding plasma transfusion had a mean INR value 1.8+1.7 (INR + SD). The mean overall reduction after 1-24 hours of plasma transfusion was -0.5+1.6 . Conclusions and Relevance: A significant amount of plasma is transfused inappropriately, leading to potential patient harm, significant unnecessary costs, and diversion of plasma away from fractionation impacting the supply of intravenous immunoglobulin. This study will inform a large quality improvement study aimed at reducing unnecessary plasma transfusion. Disclosures Heddle: Novartis: Research Funding. Arnold:Principia: Consultancy; Bristol-Myers Squibb: Research Funding; Novartis: Honoraria, Research Funding; Rigel: Consultancy, Research Funding. Hsia:Amgen: Honoraria; Jansen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.

Background Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. The majority of the literature involves adult patients. The main objective of this study was to characterize the demographic features, clinical presentation, patient outcomes, and antibody profiles of TRALI patients reported to the Canadian Blood Service (CBS) and to assess similarities and differences between adult and pediatric TRALI cases. Study Design and Methods A retrospective review of cases of TRALI submitted to the CBS from 2001 to 2011 was performed. Information collected included recipient demographics, event details, blood component transfused, morbidity and mortality data, and donor antibody results. Results A total of 284 cases of definite, possible, or probable TRALI were reported. Six percent (n = 17) occurred in children. There were no significant differences between pediatric or adult patients with TRALI. Most of the children who presented with TRALI were either teenagers or less than 1 year of age. The incident rate of reported TRALI cases in Canada per 100,000 red blood cell transfusions was estimated at 5.58 for children and 3.75 for adults. Conclusions This study is the largest case series of reported TRALI cases in children. Crude modeling suggests that the incidence of TRALI in children is similar to that of adults. Although the numbers are small, there do not appear to be differences in presentation or outcome between adults and children with TRALI. TRALI is associated with significant morbidity and mortality and pediatricians need to consider this diagnosis in children who experience respiratory distress after transfusions.

Contamination of platelet concentrates (PCs) with Staphylococcus aureus is one of the most significant ongoing transfusion safety risks in developed countries.This report describes a transfusion reaction in an elderly patient diagnosed with acute myeloid leukemia, transfused with a 4-day-old buffy coat PC through a central venous catheter. The transfusion was interrupted when a large fibrous clot in the PC obstructed infusion pump flow. Shortly afterward, a red blood cell (RBC) unit transfusion started. After septic symptoms were developed, the RBC transfusion was also interrupted. While the RBC unit tested negative for bacterial contamination, the PC and the patient samples were found to be contaminated with a S. aureus strain that exhibited the same phenotypic and genome sequencing profiles. The isolated S. aureus forms biofilms and produces the superantigen enterotoxin-like U, which was detected in a sample of the transfused PCs. The patient received posttransfusion antibiotic treatment and had her original central line removed and replaced.As the implicated PC had been tested for bacterial contamination during routine screening yielding negative results, this is a false-negative transfusion sepsis case. Using a point-of-care test could have prevented the transfusion reaction. This report highlights the increasing incidence of S. aureus as a major PC contaminant with grave clinical implications. Importantly, S. aureus is able to interact with platelet components resulting in visible changes in PCs.Visual inspection of blood components before transfusion is an essential safety practice to interdict the transfusion of bacterially contaminated units.

Background Allogeneic natural killer (NK) cell products for treatment of solid organ malignancies were prepared by performing T (CD3+)-cell depletion on nonmobilized apheresis mononuclear cell collections. The products were not B-cell depleted. This report details two cases of passenger lymphocyte syndrome (PLS) after NK-cell infusion. Case Reports Patient 1 is a blood group A+ 56-year-old female with Stage IV ovarian carcinoma who received NK cells from an O+ donor. On Day +7 she developed new hemolytic anemia. Direct antiglobulin test (DAT) was positive for immunoglobulin G and C3, and the eluate contained anti-A. Subsequently, anti-A was identified on reverse typing. She was transfused with group O red blood cells (RBCs). By Day +12 she forward typed as O with anti-A and B on reverse typing. By Day +42, DAT was negative with only weak anti-A on reverse typing. Patient 2 is a blood group B+ 51-year-old female with metastatic lobular breast carcinoma who received NK cells from an O+ donor. On Day +7 she developed new hemolytic anemia. DAT was positive, and the eluate contained anti-A and -B. Anti-A reactivity was due to anti-A,B. The next day she developed new anti-B on reverse typing. She was transfused with O RBCs. Anti-B titer increased to a maximum of 512 on Day +12. At discharge on Day +29 her anti-B titer was still 32. Conclusions These patients developed PLS after infusion of NK cells. Because of these cases NK-cell products are now B (CD19+)-cell depleted at our institution, and this approach is recommended for other centers.

This is the second published case report of Lleuprolide acetate for depot suspension (LD)-induced mania. Both reports detail a patient with a prior psychiatric history of both depressive and hypomanic episodes. While depression is a predictable and documented side effect of LD and menopause (especially in those with a previous history of symptoms), manic reactions are rare and unexplained. Possible causative mechanisms behind the LD-induced manic episodes are discussed, and we suggest that patients with a single previous hypomanic episode are at risk for LD-induced mania.

BACKGROUND: Septic transfusion reactions to apheresis platelets (PLTs) continue to occur despite preventive measures. This study evaluated the effect of two operational changes designed to reduce bacterial risk: 1) introducing inlet-line sample diversion on two-arm procedures and 2) increasing the sample volume cultured from 4 to 8 mL from all donations. STUDY DESIGN AND METHODS: Aerobic culture results and septic transfusion reactions reported between December 1, 2006, and July 31, 2008 (Period 2), were compared to March 1, 2004, to May 31, 2006 (Period 1). RESULTS: During Period 2, a total of 781,936 apheresis PLT collections were cultured, of which 130 donations (1:6015) were confirmed positive and 9 (1:86,882) had negative culture results but were associated with 11 septic reactions. Confirmed-positive cultures from two-arm procedures decreased (27.2 to 14.7 per 105 collections; odds ratio [OR], 0.54; 95% confidence interval [CI], 0.41-0.70) in Period 2, owing to a lower rate of skin flora contamination. Detection of contamination of one-arm collections significantly increased by 54% in Period 2 (13.7 vs. 21.1 per 105 collections; OR, 1.54; 95% CI, 1.05-2.27). Fewer septic transfusion reactions occurred in Period 2, but the difference did not reach significance (1.7 vs. 1.2 per 105 donations; OR, 0.68; 95% CI, 0.30-1.53). CONCLUSION: Inlet-line diversion decreased bacterial contamination during two-arm collections by more than 46%. Concurrently, doubling the sample volume was associated with a 54% relative increase in culture sensitivity. These interventions act cooperatively to decrease bacterial risk.

We developed a personal digital assistant-based knowledgebase of surgical pathology report content recommendations and performed an experimental trial to test if the knowledgebase improved report completeness. The 15 experimental group and 13 control group residents were given microscope slides and corresponding reports with the final diagnosis section blanked-out, and were asked to complete the final diagnosis section during 3 study episodes (T0, T1, and T2). At T0 (baseline), experimental group and control group produced reports of comparable completeness. During T1, experimental group was allowed to use the knowledgebase while completing reports. During T1, experimental group produced more complete reports and were better judges of report completeness than control group. At T2, when neither group used the knowledgebase, experimental group's performance was still statistically better than control group's. Use of the knowledgebase did not ensure report completeness, but was associated with more complete reports and more accurate judgments of report completeness, and this performance advantage persisted in the absence of the knowledgebase.

The purpose of this review is to provide an overview of concepts recently presented in the literature that impact our understanding of transfusion related acute lung injury (TRALI) and transfusion associated circulatory overload (TACO), and how to distinguish between the two disorders.An exceptionally clear review article by Brux and Sachs clarified the two-hit model of TRALI pathogenesis. The TRALI definition developed at the 2004 consensus conference helped demonstrate that TRALI is likely underreported. Brain natriuretic peptide can be useful in distinguishing cardiogenic from noncardiogenic pulmonary edema. Blood centers are implementing male predominant plasma programs to limit TRALI, and preliminary evidence suggests that this is a useful intervention.TACO and TRALI have emerged as important causes of posttransfusion morbidity and mortality. As understanding of their pathogenesis improves, incidence, risk factors, differences, and possible preventive interventions are becoming clearer. There is no sentinel feature that distinguishes TRALI from TACO. Developing a thorough clinical profile including presenting signs and symptoms, fluid status, cardiac status including measurement of brain natriuretic peptide, and leukocyte antibody testing is the best strategy currently available to distinguish the two disorders.

Individuals with lupus anticoagulants (LA) are at risk for thromboembolism (TE). Chronic inflammation is an important characteristic in LA patients which may dispose for TE. Platelets play a key role in inflammation and TE. We therefore investigated gene polymorphisms as well as plasma levels of platelet receptors as predictors of TE in 107 LA patients. We compared 74 patients with a history of thromboembolic disease (TE+), 56 with venous thrombosis (VT), 12 with arterial thrombosis (AT), and six patients who had both, with 33 LA patients without previous thrombosis (TE-). The P-selectin Pro715 allele was slightly more frequent in VT (OR = 3.167,95% CI 0.955-10.503; p = 0.0594), but no patient with AT had this allele (OR = 0.099, 95 % CI 0.001-0.790; p = 0.0238) which therefore may protect from AT. Plasma levels of P-selectin, collected a median of 35 months (range 2-329 months) after the last thrombotic event, were higher in patients withVT (p = 0.0096) than in TE-, but not with AT (p = 0.4713). These high P-selectin levels were not explained by the P-selectin polymorphism. The CA repeat polymorphism in the 3'-noncoding region of CD154 was significantly associated with the development of AT (OR = 4.035,95 % CI 1.329-12.249; p = 0.0138). Plasma levels of CD154 were not significantly different among the subgroups. Thus, the Thr715Pro polymorphism of P-selectin and CA repeats of CD154 are differentiating between the risk for VT and AT. Further, soluble P-selectin is elevated in LA patients with previous VT, but its role to predict VT needs to be evaluated in prospective studies.

To establish the effect of a quality control failure on the performance of the LCx-GC nucleic-acid amplification assay for Neisseria gonorrhoeae (Abbott Laboratories, Abbott Park, IL) in the field, we conducted a retrospective analysis comparing the clinical and analytic performance of the recalled lots with those not implicated in the recall. Our analysis revealed no statistically significant differences between recalled lots (n = 8,686 tests) and nonrecalled lots (n = 8,699 tests) with respect to multiple parameters of assay performance, including frequency distribution of patient results ( P = .575), prevalence of indeterminate results ( P = .245), mean positive control signals ( P = .26), and within-run calibrator precision ( P = .68). The LCx-GC system’s lack of an electronic data storage and retrieval capability prevented assessment of the impact of the quality control failure on the clinical performance of recalled lots, such as the one described herein, from being conducted in real time.

Papanicolaou (Pap) test discrepancy rates between cytotechnologists (CTs) and cytopathologists (CPs) are often kept to evaluate the performance of individual CTs. This is based on the unproven assumption that the CP's diagnoses are more likely to be correct. We investigated this assumption using data from our discrepancy files and comparing them to follow-up histology. All Pap test discrepancies were noted between January 1, 2001-December 31, 2001. Surgical pathology files were then searched for follow-up histology within 9 mo of the Pap test. Histologic diagnoses were compared with the previous CT and CP diagnoses, and then judged regarding accuracy. In total, 63,376 Pap tests were evaluated between January 1, 2001-December 31, 2001. There were 795 discrepancies throughout this period (1.25%). One hundred and sixty-six cases with discrepancies had follow-up histology within 9 mo of the Pap test (20.9%). Of downgraded cases (103), CPs were more correct in 51 cases (49.5%), whereas CTs were more correct in 52 cases (50.5%). Of upgraded cases (63), CPs were more correct in 19 cases (30.2%), whereas CTs were more correct in 44 cases (69.8%). Our results suggest that CPs are not more likely to be correct than CTs when there is a discrepancy with the diagnosis of a Pap test, especially when CPs upgrade CT diagnoses. This suggests that discrepancy data may be helpful for evaluating the performance of both CPs and CTs. It may also be of educational use for both CPs and CTs to know the follow-up histology in these cases.

To determine the incidence and prognostic value of increased serum cardiac troponin I and T concentrations over 12 months in chronic hemodialysis patients, we performed a retrospective chart review in 16 patients undergoing chronic renal hemodialysis randomly selected from the Regional Kidney Disease Program without prior knowledge of their cardiac status. Serum markers of myocardial injury (cardiac troponin I [cTnI], cardiac troponin T [cTnT], and creatine kinase MB [CK-MB]) were measured and clinical outcomes were assessed. At the beginning of the study, 12 of 16 (75%) patients had increased serum enzyme-linked immunosorbent assay (ELISA) cTnT concentrations greater than 0.20 micrograms/L, eight (50%) had increased serum CK-MB greater than 5.0 micrograms/L, and three (19%) had an increased cTnI greater than 0.8 micrograms/L. Over the 1-year study period, the cardiac event rate (n = 4 with fatal myocardial infarction) was correlated to the patients who displayed the higher elevations of cTnT, CK-MB, and cTnI. In the remaining 12 patients studied at the end of 1 year, seven (58%) had increased ELISA cTnT levels and five (42%) had increased CK-MB levels; no patients had elevated cTnI levels. Reanalysis of ELISA cTnT values with a newly formulated Enzymun cTnT assay showed no significant differences. Our data suggest that whereas substantial increases in cardiac markers tended to have a poor prognostic outcome, there was a high incidence of increased cTnT and CK-MB concentrations without evidence of myocardial injury in chronic hemodialysis patients. The lack of absolute cardiospecificity of cTnT and CK-MB may prove cTnI to be the desired serum marker for the detection of myocardial injury in patients with chronic renal disease.

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. The majority of the literature involves adult patients. The main objective of this study was to characterize the demographic features, clinical presentation, patient outcomes, and antibody profiles of TRALI patients reported to the Canadian Blood Service (CBS) and to assess similarities and differences between adult and pediatric TRALI cases.A retrospective review of cases of TRALI submitted to the CBS from 2001 to 2011 was performed. Information collected included recipient demographics, event details, blood component transfused, morbidity and mortality data, and donor antibody results.A total of 284 cases of definite, possible, or probable TRALI were reported. Six percent (n = 17) occurred in children. There were no significant differences between pediatric or adult patients with TRALI. Most of the children who presented with TRALI were either teenagers or less than 1 year of age. The incident rate of reported TRALI cases in Canada per 100,000 red blood cell transfusions was estimated at 5.58 for children and 3.75 for adults.This study is the largest case series of reported TRALI cases in children. Crude modeling suggests that the incidence of TRALI in children is similar to that of adults. Although the numbers are small, there do not appear to be differences in presentation or outcome between adults and children with TRALI. TRALI is associated with significant morbidity and mortality and pediatricians need to consider this diagnosis in children who experience respiratory distress after transfusions.

We conducted a reliability study comparing single data entry (SE) into a Microsoft Excel spreadsheet to entry using the existing forms (EF) feature of the Teleforms software system, in which optical character recognition is used to capture data off of paper forms designed in non-Teleforms software programs. We compared the transcription of data from multiple paper forms from over 100 research participants representing almost 20,000 data entry fields. Error rates for SE were significantly lower than those for EF, so we chose SE for data entry in our study. Data transcription strategies from paper to electronic format should be chosen based on evidence from formal evaluations, and their design should be contemplated during the paper forms development stage.

Papanicolaou (Pap) test discrepancy rates between cytotechnologists (CTs) and cytopathologists (CPs) are often kept to evaluate the performance of individual CTs. This is based on the unproven assumption that the CP's diagnoses are more likely to be correct. We investigated this assumption using data from our discrepancy files and comparing them to follow-up histology. All Pap test discrepancies were noted between January 1, 2001-December 31, 2001. Surgical pathology files were then searched for follow-up histology within 9 mo of the Pap test. Histologic diagnoses were compared with the previous CT and CP diagnoses, and then judged regarding accuracy. In total, 63,376 Pap tests were evaluated between January 1, 2001-December 31, 2001. There were 795 discrepancies throughout this period (1.25%). One hundred and sixty-six cases with discrepancies had follow-up histology within 9 mo of the Pap test (20.9%). Of downgraded cases (103), CPs were more correct in 51 cases (49.5%), whereas CTs were more correct in 52 cases (50.5%). Of upgraded cases (63), CPs were more correct in 19 cases (30.2%), whereas CTs were more correct in 44 cases (69.8%). Our results suggest that CPs are not more likely to be correct than CTs when there is a discrepancy with the diagnosis of a Pap test, especially when CPs upgrade CT diagnoses. This suggests that discrepancy data may be helpful for evaluating the performance of both CPs and CTs. It may also be of educational use for both CPs and CTs to know the follow-up histology in these cases.

To determine whether certain histologic features are more common in cutaneous squamous cell carcinomas (CSCCs) arising in transplant recipients than in others, we assessed several features of CSCCs from 23 patients who had not undergone transplantation and 25 transplant recipients (size, depth of invasion, sun damage, nuclear atypia, keratinization, epidermal inclusion cyst [EIC]-like features, verrucous features [VFs], shape, and mitoses per 10 high-power fields). We analyzed relationships by using chi 2 and t tests and logistic regression analysis. Transplant recipients tended to be younger than control subjects (mean [SD] age, 56.2 [14.3]; 74.1 [10.6], respectively; P.0001) and less likely to show severe sun damage (P = .0455; chi 2). CSCCs with VFs and EIC-like features were associated strongly with transplantation: odds ratio, 12.57 (95% confidence interval, 1.28-123.47; P = .0162). No other features were associated significantly with transplant status. Posttransplant tumors commonly showed verrucous and EIC-like features mimicking benign conditions. The younger age of these patients, the frequent absence of solar elastosis, and the infrequent occurrence of well-differentiated verruco-cystic CSCC in the nontransplant population suggest a different pathogenesis in the development of these neoplasms. Pathologists should be aware of this pattern, especially when diagnosing small biopsy specimens from transplant recipients.

In June 2011 the Canadian National Advisory Committee on Blood and Blood Products sponsored an international consensus conference on transfusion and trauma. A panel of 10 experts and two external advisors reviewed the current medical literature and information presented at the conference by invited international speakers and attendees. The Consensus Panel addressed six specific questions on the topic of blood transfusion in trauma. The questions focused on: ratio-based blood resuscitation in trauma patients; the impact of survivorship bias in current research conclusions; the value of nonplasma coagulation products; the role of protocols for delivery of urgent transfusion; the merits of traditional laboratory monitoring compared with measures of clot viscoelasticity; and opportunities for future research. Key findings include a lack of evidence to support the use of 1:1:1 blood component ratios as the standard of care, the importance of early use of tranexamic acid, the expected value of an organized response plan, and the recommendation for an integrated approach that includes antifibrinolytics, rapid release of red blood cells, and a foundation ratio of blood components adjusted by results from either traditional coagulation tests or clot viscoelasticity or both. The present report is intended to provide guidance to practitioners, hospitals, and policy-makers.