Canadian tertiary care pediatric massive hemorrhage protocols: a survey and comprehensive national review.

PURPOSE: Hemorrhage is the leading cause of pediatric death in trauma and cardiac arrest during surgery. Adult studies report improved patient outcomes using massive hemorrhage protocols (MHPs). Little is known about pediatric MHP adoption in Canada. METHODS: After waived research ethics approval, we conducted a survey of Canadian pediatric tertiary care hospitals to study MHP activations. Transfusion medicine directors provided hospital/patient demographic and MHP activation data. The authors extracted pediatric-specific MHP data from requested policy/procedure documents according to seven predefined MHP domains based on the literature. We also surveyed educational and audit tools. The analysis only included MHPs with pediatric-specific content. RESULTS: The survey included 18 sites (100% response rate). Only 13/18 hospitals had pediatric-specific MHP content: eight were dedicated pediatric hospitals, two were combined pediatric/obstetrical hospitals, and three were combined pediatric/adult hospitals. Trauma was the most common indication for MHP activation (54%), typically based on a specific blood volume anticipated/transfused over time (10/13 sites). Transport container content was variable. Plasma and platelets were usually not in the first container. There was little emphasis on balanced plasma/platelet to red-blood-cell ratios, and most sites (12/13) rapidly incorporated laboratory-guided goal-directed transfusion. Transfusion thresholds were consistent with recent guidelines. All protocols used tranexamic acid and eight sites used an audit tool. DISCUSSION/CONCLUSION: Pediatric MHP content was highly variable. Activation demographics suggest underuse in nontrauma settings. Our findings highlight the need for a consensus definition for pediatric massive hemorrhage, a validated pediatric MHP activation tool, and prospective assessment of blood component ratios. A national pediatric MHP activation repository would allow for quality improvement metrics.

RéSUMé: OBJECTIF: L'hémorragie est la principale cause de décès pédiatrique dans les cas de traumatismes et les arrêts cardiaques pendant la chirurgie. Les études menées chez l'adulte font état d'une amélioration des devenirs pour les patient·es lors de l'utilisation de protocoles d'hémorragie massive (PHM). On ne connait que peu de choses quant à l'adoption des PHM pédiatriques au Canada. MéTHODE: Après avoir été dispensés de l'approbation du comité d'éthique de la recherche, nous avons mené un sondage auprès des hôpitaux de soins tertiaires pédiatriques canadiens pour étudier les activations des PHM. Les directions responsables de la médecine transfusionnelle ont fourni des données démographiques sur les hôpitaux et la patientèle et sur l'activation des PHM. Nous avons extrait les données sur les PHM spécialement conçus pour les enfants à partir des documents de politiques et de procédures demandés selon sept domaines de PHM prédéfinis en nous fondant sur la littérature. Nous avons également examiné les outils éducatifs et de vérification. L'analyse n'a inclus que les PHM disposant d'un contenu spécifique à la pédiatrie. RéSULTATS: L'enquête comprenait 18 sites (taux de réponse de 100 %). Seuls 13/18 hôpitaux disposaient de contenu spécifique à la pédiatrie dans leurs PHM : huit étaient des hôpitaux pédiatriques dédiés, deux des hôpitaux pédiatriques/obstétricaux combinés, et trois des hôpitaux pédiatriques/adultes combinés. Le traumatisme était l'indication la plus fréquente d'activation d'un PHM (54 %), généralement fondé sur un volume sanguin spécifique anticipé/transfusé au fil du temps (10/13 sites). Le contenu du conteneur de transport était variable. Le plasma et les plaquettes n'étaient généralement inclus pas dans le premier récipient. Il n'y avait que peu d'emphase sur les ratios plasma/plaquettes et globules rouges équilibrés, et la plupart des sites (12/13) ont rapidement incorporé les protocoles de transfusion ciblée guidés par les tests sanguins de laboratoire. Les seuils de transfusion étaient conformes aux lignes directrices récentes. Tous les protocoles utilisaient de l'acide tranexamique et huit sites utilisaient un outil de vérification. DISCUSSION/CONCLUSION: Le contenu des PHM pédiatriques était très variable. Les données démographiques sur l'activation suggèrent une sous-utilisation dans les contextes non traumatiques. Nos résultats soulignent la nécessité d'une définition consensuelle de l'hémorragie massive pédiatrique, d'un outil d'activation pédiatrique validé du PHM et d'une évaluation prospective des ratios des composants sanguins. Un recueil national d'activation des PHM pédiatriques permettrait d'obtenir des mesures d'amélioration de la qualité.

The selection and preparation of red cell components for intrauterine transfusion: A national survey.

BACKGROUND AND OBJECTIVES: The practice regarding the selection and preparation of red blood cells (RBCs) for intrauterine transfusion (IUT) is variable reflecting historical practice and expert opinion rather than evidence-based recommendations. The aim of this survey was to assess Canadian hospital blood bank practice with respect to red cell IUT. MATERIALS AND METHODS: A survey was sent to nine hospital laboratories known to perform red cell IUT. Questions regarding component selection, processing, foetal pre-transfusion testing, transfusion administration, documentation and traceability were assessed. RESULTS: The median annual number of IUTs performed in Canada was 109 (interquartile range, 103-118). RBC selection criteria included allogeneic, Cytomegalovirus seronegative, irradiated, fresh units with most sites preferentially providing HbS negative, group O, RhD negative, Kell negative and units lacking the corresponding maternal antibody without extended matching to the maternal phenotype. Red cell processing varied with respect to target haematocrit, use of saline reconstitution (n = 4), use of an automated procedure for red cell concentration (n = 1) and incorporation of a wash step (n = 2). Foetal pre-transfusion testing uniformly included haemoglobin measurement, but additional serologic testing varied. A variety of strategies were used to link the IUT event to the neonate post-delivery, including the creation of a unique foetal blood bank identifier at three sites. CONCLUSION: This survey reviews current practice and highlights the need for standardized national guidelines regarding the selection and preparation of RBCs for IUT. This study has prompted a re-examination of priorities for RBC selection for IUT and highlighted strategies for transfusion traceability in this unique setting.

An online immunohematology educational resource for post-graduate hematology trainees: LearnSerology.ca.

BACKGROUND: Canadian hematology residents are required to demonstrate competencies in transfusion medicine by the end of their 2-year training. Prior evaluation of final year trainees revealed significant variation in knowledge. To address the lack of standardization in serology teaching, an online educational immunohematology resource was created and evaluated. STUDY DESIGN AND METHODS: All Canadian post-graduate trainees completing a residency program in adult hematology during the 2018/2019 academic year were invited to participate. Only trainees from one university were exposed to the program curriculum. A validated exam was administered to trainees at both exposed and unexposed sites at the start of the academic year as a pre-test and in the following year as a post-test. The effectiveness of the program was assessed by both comparing the degree of improvement from pre- to post-test, and by comparing performance on the post-test. RESULTS: 57 trainees from 13 universities completed the pre-test, and 45 trainees from 14 universities completed the post-test. A strong trend towards better performance in the exposed vs non-exposed trainees on the post-test was observed, and the difference was more pronounced, and statistically significant, when analysis was limited to two questions relating to interpretation of an antibody investigation panel. DISCUSSION: LearnSerology.ca is effective and may be potentially superior to traditional immunohematology teaching. The interactive capability of the platform can improve skills related to the resolution of red cell antibody panels.

Frequency and timing of all-cause deaths in visits involving suspected transfusion reactions, and the significance of cardiopulmonary disturbances.

BACKGROUND/OBJECTIVES: Transfusion reactions (TRs) may cause or contribute to death. Cardiopulmonary TRs are distressing, and collectively account for most transfusion fatalities, though the degree to which they alter survival more broadly is unclear. Deaths (and their timing) after TRs may provide further insights. MATERIALS/METHODS: Adult (tri-hospital network) haemovigilance data (2013-2016) recorded referrals with conclusions ranging from unrelated to transfusion (UTR) to entities such as: septic TRs, serologic/haemolytic reactions, transfusion-associated circulatory overload (TACO), transfusion-associated dyspnoea (TAD), transfusion-related acute lung injury (TRALI), allergic transfusion reaction (ATR), and others. For (in- or out-patient) visits involving suspected TRs (VISTRs), all-cause mortalities (% [95% confidence interval]) and associated time-to-death (TTD) (median days, [interquartile range]) were compared. Diagnoses were defined inclusively (possible-to-definite) or strictly (probable-to-definite). RESULTS: Of 1144 events, rank order VISTR mortality following (possible-to-definite) TRs, and associated TTDs, were led by: DHTR 33% [6-19], 1 death at 123d; TRALI 32% [15-54], 6 deaths: 3d [2-20]; BaCon 21% [14-31], 17 deaths: 10d [3-28]; TACO 18% [12-26], 23 deaths: 16d [6-28]; TAD 17% [11-26]: 18 deaths, 6d [3-12]. Higher-certainty TRs ranked similarly (DHTR 50% [9-91]; BaCon 29% [12-55], 4 deaths: 12d [3-22]; and TACO 25% [16-38], 15 deaths: 21d [6-28]). VISTR mortality after TACO or TRALI significantly exceeded ATR (3·3% [2·4-5·8], P < 0·00001) but was not different from UTR events (P = 0·3). CONCLUSIONS: Only half of cardiopulmonary TRs constituted high certainty diagnoses. Nevertheless, cardiopulmonary TRs and suspected BaCon marked higher VISTR mortality with shorter TTDs. Short (<1 week) TTDs in TAD, BaCon or TRALI imply either contributing roles in death, treatment refractoriness and/or applicable TR susceptibilities in the dying.

Neonatal red blood cell transfusion.

Transfusions are more common in premature infants with approximately 40% of low birth weight infants and up to 90% of extremely low birth weight infants requiring red blood cell transfusion. Although red blood cell transfusion can be life-saving in these preterm infants, it has been associated with higher rates of complications including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity and possibly abnormal neurodevelopment. The main objective of this review is to assess current red blood cell transfusion practices in the neonatal intensive care unit, to summarize available neonatal transfusion guidelines published in different countries and to emphasize the wide variation in transfusion thresholds that exists for red blood cell transfusion. This review also addresses certain issues specific to red blood cell processing for the neonatal population including storage time, irradiation, cytomegalovirus (CMV) prevention strategies and patient blood management. Future research avenues are proposed to better define optimal transfusion practice in neonatal intensive care units.

Clinical features and outcomes of patients with Shwachman-Diamond syndrome and myelodysplastic syndrome or acute myeloid leukaemia: a multicentre, retrospective, cohort study.

BACKGROUND: Data to inform surveillance and treatment for leukaemia predisposition syndromes are scarce and recommendations are largely based on expert opinion. This study aimed to investigate the clinical features and outcomes of patients with myelodysplastic syndrome or acute myeloid leukaemia and Shwachman-Diamond syndrome, an inherited bone marrow failure disorder with high risk of developing myeloid malignancies. METHODS: We did a multicentre, retrospective, cohort study in collaboration with the North American Shwachman-Diamond Syndrome Registry. We reviewed patient medical records from 17 centres in the USA and Canada. Patients with a genetic (biallelic mutations in the SBDS gene) or clinical diagnosis (cytopenias and pancreatic dysfunction) of Shwachman-Diamond syndrome who developed myelodysplastic syndrome or acute myeloid leukaemia were eligible without additional restriction. Medical records were reviewed between March 1, 2001, and Oct 5, 2017. Masked central review of bone marrow pathology was done if available to confirm leukaemia or myelodysplastic syndrome diagnosis. We describe the clinical features and overall survival of these patients. FINDINGS: We initially identified 37 patients with Shwachman-Diamond syndrome and myelodysplastic syndrome or acute myeloid leukaemia. 27 patients had samples available for central pathology review and were reclassified accordingly (central diagnosis concurred with local in 15 [56%] cases), 10 had no samples available and were classified based on the local review data, and 1 patient was excluded at this stage as not eligible. 36 patients were included in the analysis, of whom 10 (28%) initially presented with acute myeloid leukaemia and 26 (72%) initially presented with myelodysplastic syndrome. With a median follow-up of 4·9 years (IQR 3·9-8·4), median overall survival for patients with myelodysplastic syndrome was 7·7 years (95% CI 0·8-not reached) and 0·99 years (95% CI 0·2-2·4) for patients with acute myeloid leukaemia. Overall survival at 3 years was 11% (95% CI 1-39) for patients with leukaemia and 51% (29-68) for patients with myelodysplastic syndrome. Management and surveillance were variable. 18 (69%) of 26 patients with myelodysplastic syndrome received upfront therapy (14 haematopoietic stem cell transplantation and 4 chemotherapy), 4 (15%) patients received no treatment, 2 (8%) had unavailable data, and 2 (8%) progressed to acute myeloid leukaemia before receiving treatment. 12 patients received treatment for acute myeloid leukaemia-including the two patients initially diagnosed with myelodysplastic who progressed- two (16%) received HSCT as initial therapy and ten (83%) received chemotherapy with intent to proceed with HSCT. 33 (92%) of 36 patients (eight of ten with leukaemia and 25 of 26 with myelodysplastic syndrome) were known to have Shwachman-Diamond syndrome before development of a myeloid malignancy and could have been monitored with bone marrow surveillance. Bone marrow surveillance before myeloid malignancy diagnosis was done in three (33%) of nine patients with leukaemia for whom surveillance status was confirmed and 11 (46%) of 24 patients with myelodysplastic syndrome. Patients monitored had a 3-year overall survival of 62% (95% CI 32-82; n=14) compared with 28% (95% CI 10-50; n=19; p=0·13) without surveillance. Six (40%) of 15 patients with available longitudinal data developed myelodysplastic syndrome in the setting of stable blood counts. INTERPRETATION: Our results suggest that prognosis is poor for patients with Shwachman-Diamond syndrome and myelodysplastic syndrome or acute myeloid leukaemia owing to both therapy-resistant disease and treatment-related toxicities. Improved surveillance algorithms and risk stratification tools, studies of clonal evolution, and prospective trials are needed to inform effective prevention and treatment strategies for leukaemia predisposition in patients with Shwachman-Diamond syndrome. FUNDING: National Institute of Health.

Evaluation of immunohematology knowledge in hematology trainees.

BACKGROUND: Canadian hematology trainees are expected to attain clinical knowledge in the subject of red blood cell and platelet antigen systems and the principles of transfusion medicine. However, the relative degree of expertise required in blood bank serology is not well defined. STUDY DESIGN AND METHODS: A modified Delphi approach involving 10 Canadian hematology program directors was utilized to identify 12 relevant topics in immunohematology. A multiple-choice exam was developed and validated among hematology trainees from 13 hematology training programs across Canada. A Rasch analysis was used to determine fit of the examination before deploying the exam the following year to ascertain the level of knowledge in hematology trainees. RESULTS: The exam was piloted with 62 hematology trainees. The reliability of the exam was 0.93 with a mean item fit score of 1.01. The exam was able to discriminate between training years and self-rated expertise with better performance attained by more advanced trainees (p < 0.01). No differences were seen between geographic regions. A modified version of the exam was deployed the following year to 85 trainees, with a mean score of 58.9% ± 15.3%. Trainees scored poorest on topics concerning antibody investigations and D variants. CONCLUSION: A standardized exam for assessing hematology trainees on their expected expertise in transfusion immunohematology has been developed and can be used to assess the efficacy of educational resources provided in the subject. Trainees had a low overall mean score indicating additional educational initiatives are warranted.

Iron-Refractory Iron Deficiency Anemia May Not Lead to Neurocognitive Dysfunction: A Case Report.

Iron deficiency is a common cause of anemia (IDA) in infancy and can be associated with neurocognitive impairments. Iron-refractory IDA (IRIDA) has recently been described as an inherited cause of IDA due to loss-of-function mutations in the TMPRSS6 gene. IRIDA is characterized by a lack of response to iron replacement. Here we report a new case of IRIDA with its biological parameters and its functional consequences, including neuropsychological impact. The latter was evaluated by the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition and subtests. We report a 5-year-old French Canadian boy who was incidentally diagnosed with a severe microcytic anemia at 2 years of age (hemoglobin 52 g/L, mean corpuscular volume 50 fL). Except mild pallor, he was asymptomatic of his anemia. Although he had a slight response to intravenous iron therapy, his hemoglobin remained <92 g/L, with persistent microcytosis, low serum iron, but normal ferritin levels. Blood hepcidin level was higher than those of his parents and control (patient 11.2 nM, father 9.06 nM, mother 4.07 nM). Compound heterozygosity for TMPRSS6 paternally inherited c.1324G>A and maternally inherited c.1807G>C mutations were eventually identified. The patient had normal development and growth. Neuropsychological evaluation revealed excellent performance, with high Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition scores (ie, 82nd percentile for both global intelligence and general ability index). In conclusion, TMPRSS6 c.1807G>C in conjunction with c.1324G>A results in IRIDA. In contrast to the usual form of IDA, IRIDA may not be associated with neuropsychological deficits.