Healthcare provider's perceptions of bleeding in patients with acute leukaemia undergoing induction chemotherapy: A qualitative study.

BACKGROUND: Bleeding is a primary outcome for many transfusion-related trials in acute leukaemia (AL) patients, typically graded using the World Health Organisation (WHO) bleeding scale (clinically significant bleed (CSB) is ≥grade 2). This composite outcome fails to differentiate minor bleeds that may not be significant, poorly represents the total burden of bleeding and lacks input from healthcare providers (HCPs) and patients. As part of a multi-step project to create a better bleeding tool for trials, our objective was to identify HCPs' perspectives on the components of CSB in AL patients. STUDY DESIGN AND METHODS: Using qualitative description, we interviewed 19 physicians and nurses who care for AL patients undergoing induction chemotherapy. Participants were recruited from professional organisations, networks and social media. An inductive approach to conventional content analysis was used. RESULTS: HCPs identified features of CSB as the anatomical site of bleeding, amount of bleeding, need for intervention and changes in vital signs. Using these characteristics, bleeding events were categorised into three groups: clinically significant, could evolve into a CSB and not clinically significant. HCPs considered the patient's condition, bleeding history and clinical intuitions when deciding whether a bleed could escalate into serious bleeding. DISCUSSION: Using data from HCPs, we categorised bleeds as clinically significant, could evolve into a CSB, and not significant. A study of patients' perspectives on the importance of different kinds of bleeding is the next step to creating a bleeding definition that is informed by evidence, clinicians and patients.

An evaluation of the clinical impacts of 7-day platelets.

BACKGROUND: In August 2017, Canadian Blood Services extended the shelf-life of platelet concentrates from 5 to 7 days. The clinical impacts of this policy change remain unclear. STUDY DESIGN AND METHODS: We used a before-after retrospective design of platelet-transfused adult inpatients in Hamilton, ON, Canada. Data were captured for 18 months before (Period 1: February 2016-July 2017) and 18 months after (Period 2: September 2017-February 2019) 7-day platelet implementation. Primary outcome was absolute platelet count increment (ACI) in univariate and multivariate analyses adjusted for confounders. Data were obtained from our institution's transfusion database, Ontario's Transfusion Transmitted Injuries Surveillance System, and the blood supplier. RESULTS: Overall, 1360 patients with single dose platelet transfusions were included in Period 1 and 1211 patients in Period 2. Median age at admission was 66 years, and approximately 40% of patients underwent cardiac surgery. Using a non-inferiority margin of -10 × 109 /L, platelets transfused during the 7-day storage period were non-inferior to those transfused in the 5-day storage period [mean count difference - 4.63 × 109 /L (95% CI -7.40 to -1.87, p = 0.0001)]. However, platelet ACIs following transfusion consistently trended lower in the 7-day group for all patients and subgroups. No differences in secondary clinical outcomes were observed. Platelet expiry reduced from 8.1 to 6.3% (p < 0.0001). CONCLUSION: Platelet transfusions following 7-day storage policy were non-inferior to transfusions in the 5-day policy period, although reduced ACIs were observed. There were no increases in adverse clinical outcomes.

A retrospective analysis of haemolytic reactions to intravenous immunoglobulin using data from the Transfusion-Transmitted Injuries Surveillance System (Ontario).

BACKGROUND AND OBJECTIVES: Haemolysis can occur following intravenous immunoglobulin (IVIG) infusion. Haemovigilance data were analysed using a novel approach for including two control groups with no haemolysis to IVIG. Objectives included a summary of all reactions to IVIG, rate estimates and analysis of haemolytic reactions including risk factors. MATERIALS AND METHODS: Canadian haemovigilance data from Ontario (2013-2021), IVIG distribution and transfusion data from the blood supplier, and data from a large local transfusion registry were used. An 'other-reactions' control group included patients with IVIG reactions that were not haemolytic, and registry patients with no-reaction were the 'no-reaction controls'. Descriptive analysis and two logistic regression models for the different control groups were performed. RESULTS: One thousand one hundred and seventy reactions were included. Most common were febrile non haemolytic (26.1%), minor allergic (24.5%) and IVIG headache (15.3%) followed by haemolytic 10.9% (128/1170). Haemolytic reaction rates decreased over time: rates since 2020 estimated between 1.5 and 2.9/1000 kg IVIG used. The regression model for other-reaction controls identified two risk factors for haemolysis: non-O blood group recipients compared with group O recipients (p value = 0.0106) and IVIG dose per 10 g increase (OR 1.359; 95% CI 1.225-1.506). The model using no-reaction controls gave similar results and also showed no pre-medication was associated with a higher risk of haemolysis (OR 29.084; 95% CI 1.989-425.312). CONCLUSION: The frequency of haemolytic reactions has decreased over time. We confirmed non-O blood group recipients and IVIG dose as risk factors for haemolysis and raise the hypothesis that no pre-medication may increase the risk of haemolysis.

A prospective multi-faceted interventional study of blood bank technologist screening of red blood cell transfusion orders: The START study.

BACKGROUND: Transfusion of red blood cells (RBC) is a common procedure, which when prescribed inappropriately can result in adverse patient outcomes. This study sought to determine the impact of a multi-faceted intervention on unnecessary RBC transfusions at hospitals with a baseline appropriateness below 90%. STUDY DESIGN AND METHODS: A prospective medical chart audit of RBC transfusions was conducted across 15 hospitals. For each site, 10 RBCs per month transfused to inpatients were audited for a 5-month pre- and 10-month post-intervention period, with each transfusion adjudicated for appropriateness based on pre-set criteria. Hospitals with appropriateness rates below 90% underwent a 3-month intervention which included: adoption of standardized RBC guidelines, staff education, and prospective transfusion order screening by blood bank technologists. Proportions of RBC transfusions adjudicated as appropriate and the total number of RBC units transfused per month in the pre- and post-intervention period were examined. RESULTS: Over the 15-month audit period, at the 13 hospital sites with a baseline appropriateness below 90%, 1950 patients were audited of which 81.2% were adjudicated as appropriate. Proportions of appropriateness and single-unit orders increased from 73.5% to 85% and 46.2% to 68.2%, respectively from pre- to post-intervention (P < .0001). Pre- and post-transfusion hemoglobin levels and the total number of RBCs transfused decreased from baseline (P < .05). The median pre-transfusion hemoglobin decreased from a baseline of 72.0 g/L to 69.0 g/L in the post-intervention period (P < .0001). RBC transfusions per acute inpatient days decreased significantly in intervention hospitals, but not in control hospitals (P < .001). The intervention had no impact on patient length of stay, need for intensive care support, or in-hospital mortality. CONCLUSION: This multifaceted intervention demonstrated a marked improvement in RBC transfusion appropriateness and reduced overall RBC utilization without impacts on patient safety.

Effect of Short-Term vs. Long-Term Blood Storage on Mortality after Transfusion.

BACKGROUND: Randomized, controlled trials have suggested that the transfusion of blood after prolonged storage does not increase the risk of adverse outcomes among patients, although most of these trials were restricted to high-risk populations and were not powered to detect small but clinically important differences in mortality. We sought to find out whether the duration of blood storage would have an effect on mortality after transfusion in a general population of hospitalized patients. METHODS: In this pragmatic, randomized, controlled trial conducted at six hospitals in four countries, we randomly assigned patients who required a red-cell transfusion to receive blood that had been stored for the shortest duration (short-term storage group) or the longest duration (long-term storage group) in a 1:2 ratio. Only patients with type A or O blood were included in the primary analysis, since pilot data suggested that our goal of achieving a difference in the mean duration of blood storage of at least 10 days would not be possible with other blood types. Written informed consent was waived because all the patients received treatment consistent with the current standard of care. The primary outcome was in-hospital mortality, which was estimated by means of a logistic-regression model after adjustment for study center and patient blood type. RESULTS: From April 2012 through October 2015, a total of 31,497 patients underwent randomization. Of these patients, 6761 who did not meet all the enrollment criteria were excluded after randomization. The primary analysis included 20,858 patients with type A or O blood. Of these patients, 6936 were assigned to the short-term storage group and 13,922 to the long-term storage group. The mean storage duration was 13.0 days in the short-term storage group and 23.6 days in the long-term storage group. There were 634 deaths (9.1%) in the short-term storage group and 1213 (8.7%) in the long-term storage group (odds ratio, 1.05; 95% confidence interval [CI], 0.95 to 1.16; P=0.34). When the analysis was expanded to include the 24,736 patients with any blood type, the results were similar, with rates of death of 9.1% and 8.8%, respectively (odds ratio, 1.04; 95% CI, 0.95 to 1.14; P=0.38). Additional results were consistent in three prespecified high-risk subgroups (patients undergoing cardiovascular surgery, those admitted to intensive care, and those with cancer). CONCLUSIONS: Among patients in a general hospital population, there was no significant difference in the rate of death among those who underwent transfusion with the freshest available blood and those who underwent transfusion according to the standard practice of transfusing the oldest available blood. (Funded by the Canadian Institutes of Health Research and others; INFORM Current Controlled Trials number, ISRCTN08118744 .).

Systematic review of rituximab for autoimmune diseases: a potential alternative to intravenous immune globulin.

BACKGROUND: The anti-CD20 monoclonal antibody rituximab has immune-modulatory effects similar to intravenous immunoglobulin (IVIG). We performed a systematic review and meta-analysis to determine the efficacy and safety of rituximab in autoimmune diseases that are also treated with IVIG. STUDY DESIGN AND METHODS: The most common indications for immune modulation with IVIG, as identified from a 2012 regional audit in Canada, were chronic inflammatory demyelinating polyneuropathy (CIDP), immune thrombocytopenia (ITP), myasthenia gravis, multifocal motor neuropathy, Guillain-Barré syndrome, systemic lupus erythematosus (SLE), Sjogren's syndrome, and pemphigus vulgaris. We searched MEDLINE, EMBASE, and the Cochrane Library until July 2016 for studies evaluating rituximab in each of these conditions. The primary outcome in our meta-analysis was clinical response at 6 months as defined by disease-specific criteria in randomized trials. We also calculated pooled proportions of responders within disease types from observational studies. RESULTS: Ninety-five rituximab studies were identified: 86 were observational studies in patients with ITP (n = 1746), SLE (n = 1047), pemphigus vulgaris (n = 564), Sjogren's syndrome (n = 138), myasthenia gravis (n = 66), and CIDP (n = 31) and nine were randomized controlled trials (n = 992) in patients with ITP, SLE, and Sjogren's syndrome that compared rituximab with placebo plus standard of care. Among randomized trials, response rates were higher with rituximab (relative risk, 1.38; 95% confidence interval [CI], 1.05-1.83). The pooled proportion of rituximab responses ranged from 94% (95% CI, 88%-98%) for pemphigus vulgaris to 48% (95% CI, 30%-66%) for CIDP. Rituximab was generally well tolerated in observational studies although in the randomized trials, adverse events were more common in the rituximab group. CONCLUSION: Rituximab is an immune-modulating agent with biologic activity across many autoimmune conditions. Our data support the use of comparative trials with broad eligibility criteria to evaluate rituximab as an alternative to IVIG in autoimmune diseases.

Evaluating appropriate red blood cell transfusions: a quality audit at 10 Ontario hospitals to determine the optimal measure for assessing appropriateness.

BACKGROUND: Evaluating the appropriateness of red blood cell (RBC) transfusion requires labor-intensive medical chart audits and expert adjudication. We sought to determine the appropriateness of RBC transfusions at 10 hospitals using retrospective chart review and to determine whether simple metrics (proportion of single-unit transfusions, RBCs/100 acute inpatient days, proportion of transfusions with pretransfusion hemoglobin <80 g/L or posttransfusion hemoglobin <90 g/L) could be used as surrogate markers of appropriateness by comparing their values with the results from the audit. STUDY DESIGN AND METHODS: An initial block of 30 RBC units was dually adjudicated for appropriateness followed by additional blocks of 10 units until the difference between the cumulative percentage of appropriate RBC units in the preceding block and final block was <3%. Pearson correlation tests were used to evaluate associations between the metrics and percentages of appropriate transfusions per hospital. Two-by-two tables were used to assess the utility of the metrics to classify transfusions for appropriateness. RESULTS: Of the 498 units audited, 78% were adjudicated as appropriate (κ = 0.9603), with significant variability between institutions (p < 0.0001). Fifty audits or less were required at nine of the institutions. The values of the metrics were not found to have significant correlations with appropriateness, and the metric that misclassified the smallest proportion of transfusions for appropriateness was pretransfusion hemoglobin <80 g/L, at 24%. CONCLUSIONS: Our findings suggest that a chart audit of 50 RBC transfusions with adjudication using robust criteria is the optimal means of evaluating RBC transfusion appropriateness at an institution for benchmarking and quality-improvement initiatives.

AABB Committee Report: reducing transfusion-transmitted cytomegalovirus infections.

Transfusion-transmitted cytomegalovirus (TT-CMV) is often asymptomatic, but certain patient populations, such as very low birth weight neonates, fetuses requiring intrauterine transfusion, pregnant women, patients with primary immunodeficiencies, transplant recipients, and patients receiving chemotherapy or transplantation for malignant disease, may be at risk of life-threatening CMV infection. It is unclear whether leukoreduction of cellular blood components is sufficient to reduce TT-CMV or whether CMV serological testing adds additional benefit to leukoreduction. The AABB CMV Prevention Work Group commissioned a systematic review to address these issues and subsequently develop clinical practice guidelines. However, the data were of poor quality, and no studies of significant size have been performed for over a decade. Rather than creating guidelines of questionable utility, the Work Group (with approval of the AABB Board of Directors) voted to prepare this Committee Report. There is wide variation in practices of using leukoreduced components alone or combining CMV-serology and leukoreduction to prevent TT-CMV for at-risk patients. Other approaches may also be feasible to prevent TT-CMV, including plasma nucleic acid testing, pathogen inactivation, and patient blood management programs to reduce the frequency of inappropriate transfusions. It is unlikely that future large-scale clinical trials will be performed to determine whether leukoreduction, CMV-serology, or a combination of both is superior. Consequently, alternative strategies including pragmatic randomized controlled trials, registries, and collaborations for electronic data merging, nontraditional approaches to inform evidence, or development of a systematic approach to inform expert opinion may help to address the issue of CMV-safe blood components.

Platelet transfusion: a clinical practice guideline from the AABB.

BACKGROUND: The AABB (formerly, the American Association of Blood Banks) developed this guideline on appropriate use of platelet transfusion in adult patients. METHODS: These guidelines are based on a systematic review of randomized, clinical trials and observational studies (1900 to September 2014) that reported clinical outcomes on patients receiving prophylactic or therapeutic platelet transfusions. An expert panel reviewed the data and developed recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RECOMMENDATION 1: The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 2: The AABB suggests prophylactic platelet transfusion for patients having elective central venous catheter placement with a platelet count less than 20 × 109 cells/L. (Grade: weak recommendation; low-quality evidence). RECOMMENDATION 3: The AABB suggests prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 4: The AABB suggests prophylactic platelet transfusion for patients having major elective nonneuraxial surgery with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 5: The AABB recommends against routine prophylactic platelet transfusion for patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass. The AABB suggests platelet transfusion for patients having bypass who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 6: The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous). (Grade: uncertain recommendation; very-low-quality evidence).

The prevalence of anti-K in Canadian prenatal patients.

BACKGROUND: Anti-KEL1(K) is a major cause of hemolytic disease of the fetus and newborn. We utilized data from prenatal testing of patients in Western Canada to determine the frequency of anti-K. In Manitoba, we evaluated the frequency of transfusion as the likely cause for alloimmunization. We reviewed international practices to prevent alloimmunization. STUDY DESIGN AND METHODS: Prenatal patients undergo antibody screening using an automated testing platform and uniform testing algorithm. Data on the frequency of antibodies, transfusion history, and donor K typing were extracted from the relevant databases at Canadian Blood Services. National standards were reviewed with the help of local experts. RESULTS: Anti-K was found in 397 of 390,193 patients from 2011 to 2013 (1.02 per 1000) and was the second most frequent antibody after anti-E. In Manitoba, 26 of 75 (35%) anti-K patients had received transfusions in the province since 2001; 14 of the 26 (54%) had received at least one K+ RBC unit and three had received all K- units, while in nine, donor K typing was incomplete. Only eight of the 26 had previous pregnancies, three with K+ partners. International practice varies; however, prophylactic use of matched or K- units is standard in many European countries. CONCLUSIONS: Anti-K was found in 0.1% of prenatal patients. Although our data on the history of transfusion are incomplete, they demonstrate that transfusion with a K+ unit is a major cause of alloimmunization. Given advances in phenotyping and genotyping technologies, prophylactic matching should be considered in Canada.

Acquired hemophilia A.

Acquired hemophilia A is a rare, autoimmune disorder that is caused by autoantibodies that act as inhibitors to factor VIII. It is characterized by severe, unexpected bleeding that may be life-threatening. The incidence of acquired hemophilia A is ~ 0.2 to 1.48 cases per 1 million individuals per year. Acquired hemophilia A has been associated with several clinical conditions including pregnancy, autoimmune or collagen vascular disorders, malignancies, drugs, respiratory disorders, and infections. However, in ~ 50% of cases, no disease association is determined. Acquired hemophilia A should be suspected when a patient with no previous personal or family history of bleeding, presents with bleeding and an unexplained prolonged activated partial thromboplastin time (APTT) and other common causes of a prolonged APTT are ruled out. The treatment of acquired hemophilia A has two main goals: (1) to treat and/or prevent bleeding complications and (2) to eradicate the inhibitor. The recommended agents to be used for the treatment or prevention of bleeding in patients with acquired hemophilia A are the bypassing agents. Patients should be treated initially with corticosteroids, either alone or in combination with cyclophosphamide, to eradicate the inhibitor.

A new tool to assess bleeding severity in patients with chemotherapy-induced thrombocytopenia.

BACKGROUND: Current scales to measure bleeding in clinical trials are inadequate. The aim of this study was to develop a simple, valid, and reliable measurement tool to categorize the severity of bleeding in patients with chemotherapy-induced thrombocytopenia (CIT). STUDY DESIGN AND METHODS: Measurement theory was used to develop the Bleeding Severity Measurement Scale (BSMS) in four steps: 1) identification of the patient population, 2) item generation and reduction, 3) reviewing the items and formatting the scale, and 4) evaluation of psychometric properties. Feasibility was tested in a pilot study. Content and face validity were assessed by expert review. Psychometric evaluation included determination of intra- and interrater reliability and construct and criterion validity. RESULTS: The final BSMS defined two grades of bleeding: not clinically significant (Grade 1) and clinically significant (Grade 2). Grade 2 bleeds were defined as bleeds resulting in morbidity, requiring interventions, or directly causing death. The BSMS had excellent interrater (intraclass correlation coefficient [ICC], 0.80) and intrarater (ICC, 1.0) reliability and good construct and criterion validity. The BSMS distinguished between patients with different bleeding severities. CONCLUSION: Using rigorous methods, we designed a simple bleeding assessment tool with excellent psychometric properties for patients with CIT. Use of this scale in clinical trials should provide valid and reliable assessments of bleeding.

The effect of blood storage duration on in-hospital mortality: a randomized controlled pilot feasibility trial.

BACKGROUND: Whether the duration of storage of blood has an impact on patient outcomes remains controversial. The objective was to determine feasibility of a comparative effectiveness trial to evaluate duration of storage of blood before transfusion on in-hospital mortality. STUDY DESIGN AND METHODS: A single-center randomized controlled trial was performed at an acute care hospital in Canada between June and December 2010, involving consecutive hospitalized patients needing blood transfusion. Patients (n=910) were randomly assigned in a 1:2 ratio to receive freshest available versus standard-issue (oldest available) blood. Four feasibility criteria were measured: proportion of eligible patients randomized, contrast in age of blood between treatment groups, real-time data acquisition, and trial impact on blood outdating. In-hospital mortality was also reported. RESULTS: A total of 1075 of 1129 patients (95.2%) were eligible and 910 of 1075 (84.7%) were randomized: 309 received freshest available blood (1157 units), and 601 received standard-age blood (2369 units). Contrast in mean age of the oldest blood transfused between groups was 14.6 days: 12.0 (standard deviation [SD], 6.8) days in the fresh arm and 26.6 (SD, 7.8) days in the standard arm. Weekly recruitment and event reporting were achieved for all patients. The blood outdate rate was 0.10%. In-hospital mortality was 10.5%: 35 deaths (11.3%) in the fresh arm and 61 deaths (10.1%) in the standard arm (odds ratio, 1.13; 95% confidence interval [CI], 0.73, 1.76). CONCLUSION: It is feasible to conduct a large comparative effectiveness trial comparing the effect of freshest available versus standard-issue blood on in-hospital mortality. The wide CI around the estimate for in-hospital mortality supports the need for a large trial.

Transfusion-related acute lung injury in the Canadian paediatric population.

BACKGROUND: The incidence of transfusion-related acute lung injury (TRALI) in adults is approximately one per 5000 transfusions. The Canadian Paediatric Surveillance Program undertook the present study to determine the incidence of TRALI in the paediatric population and to describe the characteristics and outcomes of children with TRALI. METHODS: The present surveillance study was conducted over a three-year period. RESULTS: Four TRALI cases were reported, yielding an incidence rate of 1.8 per 100,000 transfusions. The degree of severity varied: in two patients, only supplemental oxygen was necessary, while the other two required mechanical ventilation. CONCLUSION: TRALI was reported much less often in the present study compared with adult studies; therefore, it needs to be determined whether TRALI occurs less frequently in children, or alternatively, whether TRALI is recognized less often in children. The possibility that neonates who undergo cardiac surgery are at greater risk of TRALI than other patients should be addressed in future studies.

HISTORIQUE: L'incidence de syndrome respiratoire aigu post transfusionnel (TRALI) est d'environ un cas sur 5 000 transfusions chez les adultes. Le Programme canadien de surveillance pédiatrique (PCSP) a entrepris cette étude pour déterminer l'incidence de TRALI dans la population pédiatrique et pour décrire les caractéristiques et le sort des enfants qui ont un TRALI. MÉTHODOLOGIE: Les chercheurs ont mené l'étude de surveillance pendant trois ans. RÉSULTATS: Quatre cas de TRALI ont été signalés, pour une incidence de 1,8 cas sur 100 000 transfusions. Le degré de gravité variait : deux patients n'ont eu besoin que d'oxygène d'appoint, tandis que les deux autres ont eu besoin d'une ventilation mécanique. CONCLUSION: Dans le cadre de cette étude, le TRALI était beaucoup moins signalé que dans les études auprès d'adultes. Il faut donc déterminer si le TRALI est moins fréquent ou s'il est moins dépisté chez les enfants. Lors de futures études, il faudra évaluer la possibilité que les nouveau-nés qui subissent une chirurgie cardiaque soient plus vulnérables au TRALI que les autres patients.

Do expert assessments converge? An exploratory case study of evaluating and managing a blood supply risk.

BACKGROUND: Examining professional assessments of a blood product recall/withdrawal and its implications for risk and public health, the paper introduces ideas about perceptions of minimal risk and its management. It also describes the context of publicly funded blood transfusion in Canada and the withdrawal event that is the basis of this study. METHODS: Interviews with 45 experts from administration, medicine, blood supply, laboratory services and risk assessment took place using a multi-level sampling framework in the aftermath of the recall. These experts either directly dealt with the withdrawal or were involved in the management of the blood supply at the national level. Data from these interviews were coded in NVivo for analysis and interpretation. Analytically, data were interpreted to derive typifications to relate interview responses to risk management heuristics. RESULTS: While all those interviewed agreed on the importance of patient safety, differences in the ways in which the risk was contextualized and explicated were discerned. Risk was seen in terms of patient safety, liability or precaution. These different risk logics are illustrated by selected quotations. CONCLUSIONS: Expert assessments did not fully converge and it is possible that these different risk logics and discourses may affect the risk management process more generally, although not necessarily in a negative way. Patient safety is not to be compromised but management of blood risk in publicly funded systems may vary. We suggest ways of managing blood risk using formal and safety case approaches.

Definition of a critical bleed in patients with immune thrombocytopenia: Communication from the ISTH SSC Subcommittee on Platelet Immunology.

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts and increased risk of bleeding. In preparation for an upcoming guideline, the ITP Emergency Management Guideline Panel, including clinical experts in hematology, emergency medicine, research methodology, and patient representatives, identified the need for a standardized definition of a critical ITP bleed. The goal of the definition was to distinguish critical bleeds from bleeds that may not require urgent treatment, typically in the context of severe thrombocytopenia. METHODS: The panel met in person and virtually to achieve consensus on the criteria for critical bleeding events among patients with ITP. Existing ITP bleeding scores and published definitions of major bleeds in patients receiving anticoagulation informed the definition of a critical ITP bleed. The Platelet Immunology Scientific Standardization Committee (SSC) of the International Society on Thrombosis and Haemostasis endorsed the definition. RESULTS: A critical ITP bleed was defined as: (a) a bleed in a critical anatomical site including intracranial, intraspinal, intraocular, retroperitoneal, pericardial, or intramuscular with compartment syndrome; or (2) an ongoing bleed that results in hemodynamic instability or respiratory compromise. CONCLUSION: The definition of a critical ITP bleed was developed by the ITP Emergency Management Guideline Panel and endorsed by the Platelet Immunology SSC. It incorporates both anatomic and physiologic risk and pertains to patients with confirmed or suspected ITP who typically have severe thrombocytopenia (platelet count below 20 × 109 /L).

A Canadian phase II study evaluating the efficacy of rituximab in the management of patients with relapsed/refractory thrombotic thrombocytopenic purpura.

Rituximab is a chimeric monoclonal antibody that targets the human CD-20 antigen present on malignant and normal B lymphocytes. Recent clinical studies have shown a significant response rate when this drug is given to selected patients with thrombotic thrombocytopenic purpura (TTP). Given that the clinical manifestations of TTP may be the direct result of an auto-antibody against a regulatory Von Willebrand factor enzyme (ADAMTS13), it makes biological sense to consider a therapy that has the ability to diminish or eradicate antibody-producing B cells. Despite initial positive results, there is a need to identify which patients derive durable benefit from this agent. As in other conditions that utilize therapeutic immunosuppression, there is a risk that the addition of rituximab may also lead to serious opportunistic infections.

Factors affecting the frequency of red blood cell outdates: an approach to establish benchmarking targets.

BACKGROUND: Benchmarking is a useful tool to identify best practices and to compare an organization's performance with that of similar peers, allowing for continuous quality improvement. In this study, a provincial database of red blood cell (RBC) product inventory/disposition in hospitals was analyzed to identify factors that affected RBC outdates and to systematically establish optimal target levels for RBC outdates. STUDY DESIGN AND METHODS: RBC inventory/disposition data for a 21-month period from 156 hospitals were analyzed using logistic regression techniques to identify factors that affected RBC outdating (month of the year, distance from the blood supplier, monthly transfusion activity, hospital type, and provincial region). The results were used to categorize hospitals into groupings that accounted for the factors affecting wastage. Within each grouping, the lower quartile was selected as the optimal target threshold. RESULTS: Three factors were identified as significantly affecting RBC outdating: distance from the blood supplier, mean monthly transfusion activity, and month of the year. Accounting for these variables, three hospital groupings were identified and benchmarking targets were established for mean monthly RBC outdating: There were 73 hospitals in Group 1 and their target level was 0.4 percent, 59 hospitals in Group 2 with a target of 1.1 percent, and 24 hospitals in Group 3 with a target of 20.3 percent. CONCLUSION: A method is described for establishing evidence-based benchmarking targets for RBC outdating that allows for hospitals to be grouped with similar peers taking into account logistic factors that impact on product outdating.

On-label versus off-label use of recombinant activated factor VII: a comprehensive review of use in two Canadian centers.

Recombinant activated factor VII (rFVIIa; NovoSeven, NiaStase, Novo Nordisk, Bagsvaerd, Denmark) was originally developed for the treatment of bleeds in patients with hemophilia and inhibitors. However, the agent is increasingly being employed in "off-label"/unlicensed indications. Consequently there is a need to undertake comprehensive reviews of rFVIIa use; the resulting information will facilitate understanding of how the agent is currently being employed and help to determine trends in its use. This article considers two recently reported reviews describing the use of rFVIIa in two heavily populated regions of Canada--regions with a combined population capture area of approximately 8.5 million people. The reviews report rFVIIa use in a total of 196 patients who collectively received 15,262.8 mg of rFVIIa. Both reviews obtained similar findings and reached similar conclusions: the majority of patients receiving rFVIIa are being treated for "off-label" indications, with numbers of such patients having grown rapidly between the years 2000 and 2005. However, hemophilia patients still account for the vast majority of rFVIIa use, as small numbers of hemophilia patients can consume large quantities of the agent. It is important to be aware of the increasing use of rFVIIa in off-label indications.