How do we achieve blinding in modern electronic and paper medical records during the conduct of transfusion trials?

BACKGROUND: Regulatory aspects of transfusion medicine add complexity in blinded transfusion trials when considering various electronic record keeping software and blood administration processes. The aim of this study is to explore strategies when blinding transfusion components and products in paper and electronic medical records. METHODS: Surveys were collected and interviews were conducted for 18 sites across various jurisdictions in North America to determine solutions applied in previous transfusion randomized control trials. RESULTS: Sixteen responses were collected of which 11 had previously participated in a transfusion randomized control trial. Various solutions were reported which were specific to the laboratory information system (LIS) and electronic medical record (EMR) combinations although solutions could be grouped into four categories which included the creation of a study product code in the LIS, preventing the transmission of data from the LIS to the EMR, utilizing specialized stickers and labels to conceal product containers and documents in the paper records, and modified bedside procedures and documentation. DISCUSSION: LIS and EMR combinations varied across sites, so it was not possible to determine combination-specific solutions. The study was able to highlight solutions that may be emphasized in future iterations of LIS and EMR software as well as procedural changes that may minimize the risk of unblinding.

International Survey of the Management of Disseminated Intravascular Coagulation Among Pediatric and Neonatal Health Care Practitioners.

The International Society of Thrombosis and Hemostasis (ISTH) provides objective disseminated intravascular coagulation (DIC) measurement through diagnostic criteria validated in adults. The applicability of these criteria in pediatric and neonatal DIC is controversial and unvalidated. Primary objective: to evaluate current practice in pediatric and neonatal DIC management among different specialties. Secondary objective: to understand the potential impact of developmental hemostasis on DIC laboratory evaluation. We performed a multicenter survey between January and September 2016. The questionnaire was distributed internationally through professional societies. In all, 211 responses were received, of which 160 were full responses and 51 were partial. Overall, 85% of respondents practiced in tertiary academic centers; 70% practiced in pediatric-only hospitals. The majority of respondents (42%) used their personal clinical experience in the management of DIC. Sixty percent of respondents treated DIC until the resolution of both clinical and laboratory parameters. Laboratory investigations were monitored in the majority of DIC cases without thrombosis or bleeding (80%); age-specific reference ranges for tests were lacking in 20% of pediatric-only hospitals and 35% of combined pediatric/adult hospitals. Adherence to standardized DIC guidelines was poor but varied by geographical location. This survey reveals variable practices among pediatricians in the management of DIC. Further studies are needed to validate the DIC diagnostic criteria in children.

Understanding the nursing practices and perspectives of transfusion reaction reporting.

AIMS AND OBJECTIVES: The aim of this study was to investigate nurse perspectives on transfusion-related adverse reaction reporting practices. BACKGROUND: Transfusion-related adverse reaction reporting is an essential component of hemovigilance in Canada, but reporting rates vary and under-reporting of minor transfusion-related adverse reactions exists. To our knowledge, this is the first report of nursing transfusion-related adverse reaction reporting attitudes. DESIGN: This qualitative descriptive study explored the nursing practices and perspectives of transfusion-related adverse reaction reporting by conducting one-on-one interviews with nurses (n = 25) working in adult oncology inpatient and outpatient units. METHODS: Data were thematically analysed; data collection ended when saturation was reached. The COREQ checklist was used to guide this study. RESULTS: The study revealed that the nursing practices of transfusion-related adverse reaction reporting are not standardised to meet the institutional reporting guidelines. Under-reporting of febrile reactions exists at this institution. Major concepts uncovered included the factors impacting nurses' transfusion-related reporting practices, as well as barriers and facilitators to transfusion reporting. CONCLUSION: A practice change in transfusion-related adverse reaction reporting is needed to achieve optimal hemovigilance at this institution. Using the barriers and facilitators identified in this study, institutions can better inform future interventions by employing strategies like TR reporting education in order to improve reporting of transfusion-related adverse reactions in this hospital and other similar institutions. RELEVANCE TO CLINICAL PRACTICE: This study informs clinical practice and decision-making for nurses and nursing educators who manage blood transfusion administration procedures.

Plasma transfusion practices: A multicentre electronic audit.

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Necrotizing enterocolitis and mortality after transfusion of ABO non-identical blood.

BACKGROUND: The relationship between ABO non-identical transfusion and the outcomes of necrotizing enterocolitis (NEC), and all-cause mortality in very-low birth weight (VLBW) neonates receiving red blood cell transfusion is unknown. STUDY DESIGN AND METHODS: A retrospective multicenter cohort study was conducted in VLBW neonates in neonatal intensive care units between 2004 and 2016. VLBW (≤1500 grams) neonates were followed until discharge or in-hospital death. The primary exposure was ABO group. Secondary exposures included platelet count, plasma transfusions, and maternal ABO group. Outcome measures were NEC (defined as Bell stage ≥ 2) and all-cause mortality. Time-dependent Cox regression models with competing risks were used to investigate factors associated with NEC and mortality. RESULTS: Thousand and sixteen neonates were included with 10.8% developing NEC (n = 110) and 14.1% mortality (n = 143). Platelet count (hazard ratio [HR] = 0.995; 95% confidence interval [CI]: 0.922-0.998) and number of plasma transfusions (HR = 2.908; 95% CI:1.265-6.682) were associated with NEC, while ABO group (non-O vs. O) was not (HR = 0.761; 95% CI: 0.393-1.471). Higher all-cause mortality occurred in neonates without NEC who were non-O compared with O (HR = 17.5; 95% CI: 1.784-171.692), but not in neonates with NEC (HR = 1.112; 95% CI: 0.142-8.841). Plasma transfusion was associated with increased mortality in both groups. DISCUSSION: ABO non-identical transfusion was not associated with NEC or mortality in neonates with NEC. It was associated with increased mortality in neonates without NEC. As many neonatal intensive care units transfuse only O group blood as routine practice, future trials are needed to investigate the association between this practice and neonatal mortality.

Peripartum hyperhemolysis prophylaxis and management in sickle cell disease: A case report and narrative review.

BACKGROUND: Sickle cell disease (SCD) is associated with hematologic complications including delayed hemolytic transfusion reactions (DHTRs) and pregnancy-related morbidity and mortality. Hyperhemolysis syndrome (HS) is the most severe form of DHTR in patients with SCD, in which both transfused and native red blood cells are destroyed. Further transfusions are avoided after a history of HS. Immunosuppressive agents can be used as prophylaxis against life-threatening hemolysis when transfusion is necessary. There is a paucity of evidence for the use of HS prophylaxis before transfusions, the continuation of hydroxyurea (HU) in lieu of chronic transfusion, and the use of erythropoiesis-stimulating agents (ESA) in pregnant SCD patients. CASE REPORT: We present a case of a pregnant patient with SCD and a previous history of HS. HS prophylaxis was given before transfusion with corticosteroids, intravenous immunoglobulin, and rituximab. In addition, HU was continued during pregnancy to control SCD, along with the use of concomitant ESA to maintain adequate hemoglobin levels and avoid transfusion. We describe a multidisciplinary approach to pregnancy and delivery management including tailored anesthetic and obstetric planning. CONCLUSION: This is the first published case of HS prophylaxis in a pregnant SCD patient, with good maternal and fetal outcomes after transfusion. HU and ESAs were able to control SCD and mitigate anemia in lieu of prophylactic transfusions during pregnancy. Further prospective studies are necessary to elucidate the ideal management of pregnant SCD patients with a history of HS or other contraindications to chronic transfusion.

Premedication for the prevention of nonhemolytic transfusion reactions: a systematic review and meta-analysis.

BACKGROUND: The efficacy of premedication for the prevention of nonhemolytic transfusion reactions remains controversial. This systematic review and meta-analysis assessed the effect of premedication on the rate of nonhemolytic transfusion reactions after allogeneic blood transfusion. STUDY DESIGN AND METHODS: We searched the literature using CENTRAL, MEDLINE, EMBASE, ISI Web of Science, and clinicaltrials.gov databases from inception until October 31, 2018. We included all randomized controlled trials comparing premedication to placebo or no treatment in patients receiving any labile blood product. Outcome measures were reported as relative risks (RRs) with 95% confidence intervals (CIs). Data were combined for similar outcomes where appropriate using a random-effects model. Analyses were done at both the patient and transfusion level. RESULTS: Three randomized trials using acetaminophen and antihistamine as premedication met the inclusion criteria. A total of 517 patients received 4444 red blood cell or platelet transfusions. Pooled patient-level estimates with premedication for all nonhemolytic, febrile nonhemolytic, and minor allergic reactions were RR, 0.92 (95% CI, 0.63-1.35); RR, 0.54 (95% CI, 0.26-1.1); and RR, 1.37 (95% CI 0.81-2.31), respectively. Transfusion-level analyses also showed no benefit with premedication. Of 517 patients randomized, only 27 (5.2%) had a history of transfusion reactions. CONCLUSION: Routine premedication with acetaminophen and antihistamines did not prevent nonhemolytic transfusion reactions; however, the estimate of effect was greatest for febrile reactions. The impact of premedication in patients with a prior history of transfusion reactions remains unknown and requires further evaluation in future clinical trials.

Transfusion Camp: a prospective evaluation of a transfusion education program for multispecialty postgraduate trainees.

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.

A Novel Human ß-Globin Gene Variant [Hb London-Ontario, HBB: c.332T>G] is Associated with Transfusion-Dependent Anemia in a Patient with a Hemoglobin Electrophoresis Pattern Consistent with ß-Thalassemia Trait.

We present the case of a novel ß-globin gene variant associated with early-onset transfusion-dependent anemia compatible with a ß-thalassemia major (ß-TM) phenotype in a patient of British descent. As a child, our patient developed chronic symptomatic anemia with hemoglobin (Hb) nadirs of 3.0 g/dL. She started receiving occasional transfusions by the age of 13 years and became transfusion-dependent by the age of 32 years. Work-up performed at our center showed a Hb electrophoresis compatible with ß-thalassemia (ß-thal) trait. Polymerase chain reaction (PCR) of the ß-globin gene detected a novel mutation situated at codon 110 (CTG). This missense mutation led to a substitution of the thymine nucleotide (nt) base for guanine (CGG) at position 332 (HBB: c.332T>G). We have named this new mutation Hb London-Ontario. The majority of previously described dominant allelic mutations of the ß-globin gene led to a ß-thal intermedia (ß-TI) phenotype. The heterozygous mutation which was detected in our patients is unique at it leads to a more severe ß-TM phenotype. We suspect this is a de novo mutation of which the mother of our patient, who was reported to have a form of thalassemia, was the proband.

Transfusion premedication practices among pediatric health care practitioners in Canada: results of a national survey.

BACKGROUND: Although not supported by strong evidence, premedication (pretransfusion medication) is commonly prescribed to patients who have had a transfusion reaction. The research questions were: 1) What are Canadian pediatric practitioners' views and practices regarding premedication and 2) what are barriers to reducing premedication overuse in pediatrics? STUDY DESIGN AND METHODS: An online survey targeted hematology/oncology, emergency medicine, general surgery, intensive care, and cardiac intensive care practitioners in all 16 Canadian pediatric tertiary hospitals. The survey included four sections: demographic, clinical, future directions, and organizational questions. RESULTS: Fifty-five individuals from 15 of 16 pediatric tertiary care sites completed the survey: 53 physicians and two nurse practitioners. More than half of the respondents (55%; 30/55) were pediatric hematology/oncology providers, and 35% (19/55) were directors of their respective divisions. Eighty-seven percent of respondents estimated that they premedicate up to 25% of red blood cell (RBC) transfusions, and 13% premedicate 26% to 50% RBC transfusions. Proportions were similar for platelet transfusions. Most respondents reported that trainees are involved in transfusion and premedication order decisions. Seven percent believe that their hospital does not use leukoreduction and 27% are not sure. Sixty-five percent of respondents were not aware of a clinical practice guideline or a standard order set (SOS) at their institution: 51% are interested in having both available. Factors influencing the decision to premedicate and barriers to change were identified. CONCLUSION: Premedication practices are variable in Canadian pediatric academic hospitals. Evidence-based premedication clinical practice guidelines and SOS could be explored as a way to standardize practices. There were perceived educational and institutional barriers to practice change.

Triplets with neonatal alloimmune thrombocytopenia due to antibodies against human platelet antigen 1a.

BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) has been reported only rarely in twins and not at all, to our knowledge, in triplets. CASE REPORT: Nonidentical triplets were born with severe thrombocytopenia. Nadir platelet (PLT) counts were 17 × 109 , 12 × 109 , and 10 × 109 /L. NAIT was confirmed by an incompatibility for human PLT antigen (HPA)-1a and the presence of maternal anti-HPA-1a. The maternal genotype was HPA-1bb and the paternal genotype was HPA-1aa; thus, all children were affected. RESULTS: PLT counts for each infant improved with the administration of random-donor PLT transfusions. All three infants also received intravenous immunoglobulin. None had major bleeding. A small isolated subependymal hemorrhage was found incidentally in one infant; this remained stable on repeat imaging. CONCLUSIONS: This is the first report of triplets with NAIT. Anti-HPA-1a is sufficiently potent to affect three infants simultaneously. Random-donor PLTs were effective in improving PLT counts in all three infants.

Neurological PRESentations in Sickle Cell Patients Are Not Always Stroke: A Review of Posterior Reversible Encephalopathy Syndrome in Sickle Cell Disease.

Acute neurological changes in sickle cell disease (SCD) patients often raise the suspicion for stroke. Posterior reversible encephalopathy syndrome (PRES) can mimic stroke in its clinical presentation. We aimed to (i) review the PRES literature in SCD patients including clinical presentation, risk factors, pathophysiology, and management and (ii) elucidate the distinction between PRES and stroke in SCD. The exact pathophysiology of PRES in SCD remains elusive but is likely multifactorial and related to sickling, ischemia, and chronic anemia predisposing to vasogenic edema. PRES and stroke in SCD are distinguishable conditions. Our review may help elucidate a clinical approach to this distinction.

THromboprophylaxis In Sickle Cell Disease with central venous catheters (THIS): an internal pilot randomised controlled trial protocol.

INTRODUCTION: Individuals with sickle cell disease (SCD) and central venous catheters (CVC) are at high risk for venous thromboembolism (VTE). Minimal data exist regarding the use of anticoagulation as thromboprophylaxis of VTE in this demographic, and as a result, clinical equipoise exists. Prophylactic dose rivaroxaban, a direct oral anticoagulant, is efficacious and safe as thromboprophylaxis in other demographics, and may be an optimal agent in SCD with CVC. Prior to conducting a full clinical trial to assess rivaroxaban as thromboprophylaxis in SCD with CVC, a pilot study is needed to gauge its feasibility. METHODS AND ANALYSIS: THromboprophylaxis In Sickle Cell Disease pilot trial is an investigator-initiated, multicentre, double-blinded, randomised controlled trial (RCT) assessing if it is feasible and safe to conduct an adequately powered RCT comparing rivaroxaban to matching placebo as thromboprophylaxis in those with SCD and CVC. Fifty adult patients with SCD and CVC will be randomised to receive either rivaroxaban 10 mg daily or matching placebo for the duration of the CVC in situ for up to 1 year. After randomisation, follow-up visits will occur every 3 months. The primary outcomes pertain to the feasibility of a full trial and include numbers of eligible and recruited participants. Exploratory outcomes include overall incidence of VTE and bleeding complications, as well as quality of life. If the full trial is feasible, blinding will be maintained and patients in the pilot study will be included in the full trial. ETHICS AND DISSEMINATION: The trial was initially approved by the University Health Network Research Ethics Board (REB) in Toronto, Canada. All sites will obtain approval from their respective REB prior to commencement of study activities. Study results will be disseminated through presentations at medical conferences and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05033314.