Abstract: Background: Pyruvate Kinase (PK) deficiency is the most common enzyme defect of the glycolytic pathway causing hereditary non-spherocytic hemolytic anemia. Patients have a broad phenotypic spectrum, ranging from mild anemia to transfusion dependence, and there is wide variation in transfusion practices and decisions about splenectomy. No prior studies have reported on the use of validated health related quality of life (HRQoL) measures in this population. Aim: To describe patient reported outcomes including general HRQoL and fatigue in adults with PK deficiency and the correlation with clinical and laboratory features. Methods: Patients were enrolled on the PK Deficiency Natural History Study, a prospective 30 site international study. All patients had molecularly confirmed PK deficiency. Adults (n=132), ages ≥18 years, completed the EuroQol-5D (high index equivalent to better QoL), PROMIS Fatigue Short Form 7a (high scores equivalent to higher fatigue), and the Functional Assessment of Cancer Therapy-Anemia (FACT-An, high scores equivalent to less fatigue) surveys at enrollment and annually. Timing of administration was convenience based. Survey data were analyzed according to proprietary scoring guidelines. Tests of association were performed using Fisher's exact test (categorical) and Wilcoxon rank sum test (continuous). Regular transfusions were defined as ≥6 transfusions in 12 months. Genotypes were grouped as two missense mutations (M/M), one missense/one non-missense (M/NM), or two non-missense mutations (NM/NM)); non-missense included deletions or other drastic variants. The minimal important difference (MID) for the FACT-An has been reported as 7 points (Cella et al, J Pain Symptom Manage 2002). P-values 〈 0.05 were considered statistically significant. Results: At enrollment, 128 adults completed the FACT-An with a median total score of 156 (IQR 122-190). Patients receiving regular transfusions reported significantly lower FACT-An scores than those who were not regularly transfused (median 129 vs 156, p=0.004) with significantly lower scores for physical, emotional, and functional well-being and anemia sub-scores (Table). This difference also surpassed the MID. However, non- regularly transfused patients with hemoglobin (Hb) 〈 8 g/dl did not report significantly different scores than those with Hb≥ 8 g/dl (p=0.75). There were also no significant differences in FACT-An scores by splenectomy status or age. The FACT-An score differences were greater than the MID for patients with iron overload (ferritin 〉 1000 ng/dL or chelation), higher number of lifetime transfusions, and two missense mutations. Females reported significantly lower scores than males (median 143 vs. 160, p=0.006) with significantly lower anemia sub-scores (p=0.0009). FACT-An surveys completed at the one year follow-up time point validated these findings. EuroQol-5D scores (n=124) at enrollment were similar to the healthy population (median PK deficiency index score 0.88; healthy population index mean 0.88, Shaw et al, Medical Care 2005). No significant differences were found by Hb level, splenectomy status, transfusion status, or genotype group. The median PROMIS fatigue T score (n=66) was 52.1 (IQR 40.5-63.7). Similar to the FACT-An survey data, PROMIS fatigue scores were significantly worse in patients who were regularly transfused (67.0 vs 52.4, p=0.02). PROMIS fatigue scores were also significantly worse in patients ≥40 years old (p=0.05) and females (p=0.01). Conclusions: Using the FACT-An and PROMIS Fatigue measures, patients with PK deficiency who are regularly transfused report significantly more fatigue and worse HRQoL compared with those who are not transfused. Important differences were also seen by iron status and mutation group using the FACT-An. Patients report similar fatigue levels regardless of Hb level, which suggests that symptoms, rather than Hb value alone, should be factored into clinical decision making. In contrast to anemia related HRQoL scores, overall HRQoL scores using validated generic measures in patients with PK deficiency show no differences compared with the healthy population, suggesting that disease-specific measures may better detect the effects of PK deficiency on HRQoL. Disclosures Van Beers: Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Glader:Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Chonat:Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Despotovic:AmGen: Research Funding; Novartis: Research Funding; Sanofi: Consultancy. Kwiatkowski:bluebird bio: Consultancy, Honoraria, Research Funding; Agios Pharmaceuticals: Consultancy, Research Funding; Novartis: Research Funding; Apopharma: Research Funding; Terumo: Research Funding. Thompson:La Jolla Pharmaceutical: Research Funding; Baxalta/Shire: Research Funding; Novartis: Research Funding; Celgene: Research Funding; bluebird bio: Consultancy, Research Funding; Biomarin: Research Funding; Amgen: Research Funding. Newburger:TransCytos LLC: Consultancy; Janssen Research & Development, LLC: Consultancy, Honoraria; X4 Pharmaceutics: Consultancy, Honoraria. Ravindranath:AGIOS: Other: Site Investigator for Pyruvate Kinase Deficiency. Sheth:Terumo Corporation: Research Funding; Novartis: Research Funding; La Jolla Pharmaceutical Company: Research Funding; Celgene Corporation: Consultancy, Research Funding; Bluebird Bio: Consultancy. Grace:Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Research Funding; Agios Pharmaceuticals: Consultancy.

Abstract: Introduction: Pyruvate kinase (PK) deficiency causes a defect in the glycolytic pathway, leading to a hereditary hemolytic anemia. Management is supportive and consists of splenectomy, transfusions, and chelation therapy. Aim: To better understand the comorbidity and complication profile of adults with PK deficiency, and the extent to which transfusion frequency contributes, the objectives of this study were to (1) quantify the prevalence of comorbidities and complications according to transfusion history and (2) compare the types and rates of select comorbidities and complications with the general population. Methods: Data were obtained from the enrollment survey of the PK Deficiency Natural History Study (NHS), a longitudinal, retrospective and prospective cohort study in which clinical, laboratory, transfusion, and radiologic data were collected; all participants were confirmed to have 2 mutations in the PKLR gene. Patients (n=122) were eligible for this analysis if they were ≥18 years of age and had sufficient data on transfusion history to enable classification into 1 of 3 cohorts: "Ever Regularly Transfused" (ERT, defined as ≥6 transfusions in any 12-month period), "Never Regularly Transfused" (NRT, defined as having ≥1 lifetime transfusion but never having 〉 4 transfusions in any 12-month period), or "Never Transfused" (NT). To contextualize the findings, the frequencies of select conditions were compared with an age- and gender-matched cohort of individuals from the insured, general US population who did not have any hemolytic anemia diagnoses and had ≥5 years of continuous enrollment in the Truven MarketScan administrative claims database. The NHS reported lifetime prevalence rates, whereas rates obtained from the MarketScan data were based on diagnosis and procedure codes over varying look-back periods; therefore, to minimize bias, we limited PK deficiency vs. general population comparisons to (1) chronic conditions that require lifetime management and would thus still be recorded in claims data years after initial diagnosis, and/or (2) conditions for which a diagnosis/procedure date was available in the NHS and could be matched in time to the average 8-year look-back period for the general population. Frequencies were compared across mutually exclusive cohorts using Fisher's exact 2-tailed tests of significance. Results: ERT (n=65), NRT (n=30), and NT patients (n=27) had a mean age of 34.2, 39.5, and 37.2 years at enrollment, respectively (not significant [ns]), with 46.2%, 56.7%, and 59.3%, respectively, being male (ns). ERT patients trended toward being more likely than NT patients to be Amish and have the homozygous R479H splice variant (30.8% vs 11.1% [p=0.064] ) but were significantly less likely to have a missense/missense PKLR genotype (32.3% vs 70.4% [p=0.001]). Compared with the general population, patients with PK deficiency had significantly higher rates of splenectomy, cholecystectomy, osteoporosis, liver cirrhosis, pulmonary hypertension, and current prophylactic antibiotic and anticoagulant use (Table). Rates of splenectomy, cholecystectomy, and osteoporosis were significantly higher in patients with PK deficiency, regardless of transfusion cohort, and both ERT and NRT patients had significantly higher rates of liver cirrhosis than individuals from the general population. A gradient was seen across transfusion cohorts for other conditions. Notably, 83.1% of ERT patients, 50.0% of NRT patients, and 25.9% of NT patients had a history of liver iron overload. ERT patients were also significantly more likely than NRT and NT patients to have had a splenectomy, cholecystectomy, and/or thrombosis, and to currently use prophylactic antibiotics. Findings were consistent when the analysis was restricted to non-Amish patients with PK deficiency. Conclusions: Patients with PK deficiency have higher rates of select comorbidities and complications than age- and gender-matched individuals who do not have PK deficiency. Even patients with PK deficiency who have never been transfused are at increased risk of complications of the disease and its treatment. Disclosures Boscoe: Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Yan:Agios Pharmaceuticals, Inc.: Consultancy. Hedgeman:IBM Watson Health: Employment. van Beers:Agios Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Research Funding; RR Mechatronics: Research Funding. Al-Samkari:Agios: Consultancy, Research Funding; Dova: Consultancy, Research Funding; Moderna: Consultancy. Barcellini:Incyte: Consultancy; Alexion: Consultancy, Speakers Bureau; Agios Pharmaceuticals, Inc.: Consultancy; Novartis: Speakers Bureau; Apellis: Consultancy; bioverativ: Consultancy. Eber:Agios Pharmaceuticals, Inc.: Consultancy. Glader:Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Chonat:Alexion: Other: advisory board; Agios Pharmaceuticals, Inc.: Other: advisory board. Rothman:Agios: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Kuo:Agios: Consultancy; Alexion: Consultancy, Honoraria; Apellis: Consultancy; Bioverativ: Other: Data Safety Monitoring Board; Bluebird Bio: Consultancy; Celgene: Consultancy; Novartis: Consultancy, Honoraria; Pfizer: Consultancy. Kwiatkowski:Agios: Consultancy; bluebird bio, Inc.: Consultancy, Research Funding; Imara: Consultancy; Apopharma: Research Funding; Novartis: Research Funding; Celgene: Consultancy; Terumo: Research Funding. Ravindranath:Agios Pharmaceuticals, Inc.: Other: I am site PI on several Agios-sponsored studies, Research Funding. Neufeld:Octapharma, Shire Pharmaceuticals (Baxalta), Novo Nordisk, Celgene, NHLBI/NIH: Research Funding; Octapharma, Agios, Acceleron, Grifols, Pfizer, CSL Behring, Shire Pharmaceuticals (Baxalta), Novo Nordisk, ApoPharma, Genentech, Novartis, Bayer Healthcare: Consultancy; Octapharma: Other: study investigator, NuProtect study (Octapharma-sponsored). Holzhauer:Agios Pharmaceuticals, Inc.: Consultancy. Verhovsek:Sickle Cell Disease Association of Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding; Canadian Haemoglobinopathy Association: Membership on an entity's Board of Directors or advisory committees; Vertex: Consultancy; Sickle Cell Awareness Group of Ontario: Membership on an entity's Board of Directors or advisory committees. Kunz:Novartis: Membership on an entity's Board of Directors or advisory committees. Sheth:Apopharma: Other: Clinical trial DSMB; Celgene: Consultancy; CRSPR/Vertex: Other: Clinical Trial Steering committee. Despotovic:Novartis: Research Funding; Dova: Honoraria. Grace:Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding.

Abstract: Background: Pyruvate kinase deficiency (PKD) is the most common cause of chronic hereditary non-spherocytic hemolytic anemia. The spectrum of disease in PKD is broad, ranging from an incidentally discovered mild anemia to a severe transfusion-dependent anemia. Splenectomy partially ameliorates the anemia and reduces the transfusion burden in the majority of patients. Because hemoglobin poorly correlates with symptoms in PKD, transfusion requirements are typically used clinically to classify disease severity with those who are regularly transfused despite splenectomy recognized as the most severely affected subgroup. Aim: To compare demographics, complications, and laboratory results between the most severely-affected PKD patients (those that are splenectomized and regularly transfused) with non-regularly transfused splenectomized PKD patients. Methods: After ethics committee approval, patients were enrolled on the PKD Natural History Study, a prospective 30 site international study. All patients had molecularly confirmed PKD. Only splenectomized patients were included in the analysis. Transfusion frequency was observed over a 3-year period. Patients were divided into two groups based on transfusion frequency: the severe phenotype group was defined as those who receive regular transfusions (≥6 discrete red cell transfusion episodes per year) and the control group did not receive regular transfusions. Phenotype stability over the 3-year period was also assessed. Results: 154 splenectomized patients with PKD were included: 30 patients in the severe PKD phenotype group and 124 patients in the comparison PKD group. Results of the analysis comparing the two groups are described in the Table. Severely affected patients were more likely to be female (77% versus 51%, p=0.013), older at the time of splenectomy (median age: 5 versus 3.6, p=0.011), have iron overload (93% vs. 51%, p & lt;0.0001), have received chelation therapy (90% vs. 42%, p & lt;0.0001), and had more lifetime transfusions (median: 77 versus 15, p & lt;0.0001). Rates of other PKD complications including pulmonary hypertension, extramedullary hematopoiesis, liver cirrhosis, endocrinopathy, and bone fracture appear similar between the two groups. Laboratory values, including hemoglobin, total bilirubin, normalized PK enzyme activity, and median absolute reticulocyte count appear similar between the two groups. The underlying genetic mutation patterns (missense mutations versus non-missense mutations) were also similar between the groups. Phenotype stability over time was highly variable: of the patients with a severe phenotype at enrollment, 62% had a severe phenotype during the first follow-up year and 39% had a severe phenotype at the second follow-up year. Conclusions: Patients with PKD who are regularly transfused despite splenectomy appeared to have similar rates of PKD-associated complications (except for iron overload) and similar relevant laboratory values and genotypes when compared to those who are not regularly transfused after splenectomy. The similarity observed between severe phenotype patients and comparison patients with PKD may result from a protective effect of transfusion (e.g. reduction of bone fractures and extramedullary hematopoiesis) or could suggest transfusion-dependence is an artificial signifier of disease severity, reflective of provider practices and patient symptoms rather than an actual distinct phenotype. Transfusion requirements in severe PKD appear to fluctuate significantly over time. Disclosures Al-Samkari: Dova: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Moderna: Consultancy. van Beers:RR Mechatronics: Research Funding; Agios Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Research Funding. Barcellini:Agios: Consultancy, Other: Advisory board; Apellis: Consultancy; Incyte: Consultancy, Other: Advisory board; Bioverativ: Consultancy, Other: Advisory board; Novartis: Research Funding, Speakers Bureau; Alexion: Consultancy, Research Funding, Speakers Bureau. Eber:Agios Pharmaceuticals, Inc.: Consultancy. Glader:Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Chonat:Alexion: Other: advisory board; Agios Pharmaceuticals, Inc.: Other: advisory board. Kuo:Pfizer: Consultancy; Novartis: Consultancy, Honoraria; Celgene: Consultancy; Agios: Consultancy; Alexion: Consultancy, Honoraria; Apellis: Consultancy; Bioverativ: Other: Data Safety Monitoring Board; Bluebird Bio: Consultancy. Despotovic:Dova: Honoraria; Novartis: Research Funding; Amgen: Research Funding. Kwiatkowski:Celgene: Consultancy; Terumo: Research Funding; Apopharma: Research Funding; bluebird bio, Inc.: Consultancy, Research Funding; Agios: Consultancy; Imara: Consultancy; Novartis: Research Funding. Thompson:Baxalta: Research Funding; Novartis: Consultancy, Research Funding; bluebird bio, Inc.: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Ravindranath:Agios Pharmaceuticals, Inc.: Other: I am site PI on several Agios-sponsored studies, Research Funding. Rothman:Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Agios: Honoraria, Research Funding. Verhovsek:Sickle Cell Awareness Group of Ontario: Membership on an entity's Board of Directors or advisory committees; Sickle Cell Disease Association of Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding; Canadian Haemoglobinopathy Association: Membership on an entity's Board of Directors or advisory committees; Vertex: Consultancy. Kunz:Novartis: Membership on an entity's Board of Directors or advisory committees. Sheth:CRSPR/Vertex: Other: Clinical Trial Steering committee; Apopharma: Other: Clinical trial DSMB; Celgene: Consultancy. London:United Therapeutics: Consultancy; ArQule, Inc: Consultancy. Grace:Novartis: Research Funding; Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Abstract: Introduction: In North America, there are a growing number of patients with hemoglobinopathies, including sickle cell disease and thalassemia. As previously identified in needs assessment surveys of Canadian hematology training program directors and fellows (Verhovsek et. al. 2014 - https://ash.confex.com/ash/2014/webprogram/Paper71742.html), hemoglobinopathy learning constitutes an integral component of the hematology residency curriculum, however there are significant differences in volume and case-mix of hemoglobinopathy exposure among training programs. Fellows and program directors expressed strong interest in online e-learning modules to address gaps in clinical and laboratory learning. As such, we developed a set of e-learning modules for hemoglobinopathies that were implemented as a pilot study. We hypothesized that the e-learning-based curriculum would enhance education and standardize curricular exposure between Canadian hematology programs. Methods: Based on the National Hemoglobinopathy Learning Objectives, a curriculum of 12 case-based modules was developed. Modules were implemented as a pilot study in four Canadian hematology training programs using a distributed practice model - two modules every two months over the 12-month academic year. Training programs were selected based on baseline hemoglobinopathy exposure in their curriculum (two programs with high baseline exposure and two programs with low baseline exposure). Fellows completed the modules independently. Learning was supplemented with bimonthly module review sessions facilitated by expert faculty. In programs where the program directors did not identify a local faculty member with content expertise, review sessions were run by web conference. Data were collected regarding the efficacy of the intervention through three main formats: in-person fellow focus groups, online fellow questionnaires, and sets of designated hemoglobinopathy-related questions at the annual National Hematology Online Practice Exam for all Canadian Hematology fellows. Results: From online graded survey responses (1 to 5, "strongly disagree" to "strongly agree"), 97% of respondents indicated the modules were relevant to their particular learning needs (Mean 4.39, SD = 0.55). All survey respondents indicated the case scenarios were realistic, and 95% felt that the e-learning software was easy to use, engaging and offered flexibility of computer-based learning. Responses in focus group feedback sessions mirrored the survey findings: modules were described as "very useful", "realistic", and of high production quality, with participants indicating they felt the issue of variability in case mix could be addressed with online cases. With respect to the expert-led case review sessions, the majority of focus group responses indicated they were valuable and enhanced the learning obtained from online modules, with review sessions being increasingly useful with later modules that were more challenging. In addition, both online survey responses and focus group feedback identified that participants would strongly recommend the modules to their colleagues (97% of survey responses, Mean 4.43, SD = 0.56). Finally, comparing results of the annual National Hematology Online Practice exam, programs that participated in the online hemoglobinopathy modules saw their fellows achieve a higher incremental change in their score from 2015 to 2016, as compared to their counterparts who did not participate in the online modules (increase of 18.5% vs. 14.8%). Conclusion/Implications: In this pilot implementation study, online hemoglobinopathy modules were shown to have high usability and user satisfaction with content. Fellows agreed that the e-learning modules addressed current gaps in curricula and variability in case-mix exposure. Among fellows who have completed the annual National Hematology Online Practice Exam, comparison of the 2015 and 2016 exam scores in participating and non-participating programs indicated improved performance on hemoglobinopathy-related questions. Taken together, our study has shown that our proposed e-learning-based curriculum has been a successful intervention in promoting, standardizing and enhancing education in hemoglobinopathies among Canadian hematology programs. Disclosures Bates: Eli Lilly Canada: Other: Partial salary support through Eli Lilly Canada/May Cohen Chair in Women's Health.

Abstract: Alloimmunisation and haemolytic transfusion reactions (HTRs) can occur in patients with sickle cell disease (SCD) despite providing phenotype‐matched red blood cell (RBC) transfusions. Variant RBC antigen gene alleles/polymorphisms can lead to discrepancies in serological phenotyping. We evaluated differences between RBC antigen genotyping and phenotyping methods and retrospectively assessed if partial antigen expression may lead to increased risk of alloimmunisation and HTRs in SCD patients at a tertiary centre in Canada. Methods RBC antigen phenotyping and genotyping were performed by a reference laboratory on consenting SCD patients. Patient demographic, clinical and transfusion‐related data were obtained from a local transfusion registry and chart review after research ethics board approval. Results A total of 106 SCD patients were enrolled, and 91% (n = 96) showed additional clinically relevant genotyping information when compared to serological phenotyping alone. FY*02N.01 ( FY*B GATA‐1 ) (n = 95; 90%) and RH variant alleles (n = 52, 49%; majority accompanied by FY*02N.01 ) were common, the latter with putative partial antigen expression in 25 patients. Variability in genotype‐phenotype antigen prediction occurred mostly in the Rh system, notably with the e antigen (kappa: 0.17). Fifteen (14.2%) patients had a history of alloimmunisation, with five having HTR documented; no differences in clinical outcomes were found in patients with partial antigen expression. Genotype/extended‐phenotype matching strategies may have prevented alloimmunisation events. Conclusion We show a high frequency of variant alleles/polymorphisms in the SCD population, where genotyping may complement serological phenotyping. Genotyping SCD patients before transfusion may prevent alloimmunisation and HTRs, and knowledge of the FY*02N.01 variant allele increases feasibility of finding compatible blood.

Abstract: Introduction: Red blood cell (RBC) transfusion is the cornerstone of management in many patients with sickle cell disease (SCD). However, RBC transfusion can be complicated by alloimmunization and hemolytic transfusion reactions in this population despite providing extended phenotype-matched RBC transfusions. This is due to heterogeneity of RBC antigens, unique variant mutations in this population, and genetic mismatch between the blood donor pool and SCD patients in North American settings. In this study, we evaluated the level of discrepancy between RBC antigen genotyping and traditional phenotyping methods and the association of these discrepancies with the presence of RBC alloantibodies in SCD patients at our centre in Canada. Methods: Commencing in January 2015, RBC antigen genotyping has been included in the care for patients with SCD treated at our Hemoglobinopathy Clinic in an academic medical centre. Patient blood samples are sent to a reference laboratory to perform genotyping of RhCE, Kell, Kidd, Duffy, and S antigens. RBC antigen phenotyping was performed locally using both tube and automated solid phase assays. Additional clinical data, demographic and transfusion-related data were obtained from a local transfusion registry databse and thorough clinical chart reviews. Approval from our centre's research ethics board was obtained prior to commencement of data collection. Results: To date, RBC antigen genotyping has been performed on 45/88 SCD patients treated at our centre. The mean age of these patients was 25, and 58% were female. The majority of patients had HbSS SCD genotype (64.4%), or HbSC (26.7%). Overall, 32/45 (71%) of patients had variant mutations detected by genotyping, including 9 (20%) patients with more than one variant mutation. The most common mutation detected was the GATA mutation (n= 23; 51%) resulting in loss of Fyb antigen expression on RBCs, but associated with expression of Fyb on non-erythroid tissues. The RhCE system showed variant mutations resulting in partial expression of antigens in 9 (20%) patients. Alloantibodies were found in 9/36 (25%) patients with either a GATA mutation or no variant mutations. Alloantibodies were found in 2/9 (22.2%) patients with mutations resulting in partial antigen expression. The proportion of patients with any discrepancy between genotyping and phenotyping was 34/45 (75.6%). The largest rates of discordance were seen in the RhCE system, with the c antigen having a kappa of 0.68 and e antigen having a kappa of 0.32 (Table 1). Conclusion: Our results showed a high prevalence of variant mutations and significant discrepancies between genotyping and phenotyping methods, most notably in the RhCE antigen system. Mutations resulting in partial antigen expression were associated with development of alloantibodies in 22.2% of patients in our study, which may have been prevented with a genotype-based antigen-matching strategy. Additionally, knowledge of presence of GATA mutation will enhance feasibility of antigen matching for affected patients, who may have otherwise required RBC units negative for Fyb based on local policies. To our knowledge these results represent the first published data from a Canadian centre, showing similar rates of discrepancy between traditional phenotyping methods and RBC antigen genotyping as reported in other regions. Although phenotype-based matching strategies are used in many centres, these strategies can place patients with partial RBC antigen variant mutations at a direct increased risk of alloimmunization. Thus genotype-based antigen-matching strategies should be considered for transfusion of matched RBCs in patients with SCD. Table 1. Blood Group Antigen Frequency In SCD Patients By Phenotyping/Genotyping with Level of Agreement Between Both Methods Antigen Phenotype Genotype Kappa Positive Negative Positive Negative Partial C 37.78 62.22 28.89 62.22 8.89 0.82 c 88.89 11.11 80.00 11.11 8.89 0.68 E 13.33 86.67 13.33 86.67 1.00 e 97.78 2.22 88.89 2.22 8.89 0.32 Fya 13.33 86.67 13.33 86.67 1.00 Fyb 22.22 68.89 26.67 73.33 0.94 Jka 80.00 20.00 82.22 17.78 0.93 Jkb 51.11 48.89 55.56 44.44 0.91 S 28.89 42.22 46.67 53.33 1.00 s 51.11 6.67 86.67 13.33 1.00 Disclosures No relevant conflicts of interest to declare.

Abstract: The McMaster Internal Medicine International Health Elective (IHE) has been placing senior medical residents (PGY-3) in an elective setting in a teaching hospital in Kampala, Uganda, for the past 7 years. This article discusses a study in which the authors electronically mailed a survey to alumni of this elective to evaluate important aspects of program participation from the residents’ point of view. The factors most commonly cited as being important in the decision to apply to the McMaster IHE were to gain experience practising medicine in a resource-limited setting and to gain exposure to diseases and conditions not commonly encountered in Canada. Most residents (61.5%) planned to have some involvement in global health prior to their elective, and 100% felt the elective experience made them more likely to take part in global health activities in the future. IHEs offer a unique opportunity for residents to explore global health. Residents participating in this survey found the McMaster Internal Medicine IHE to be a successful endeavour.

Abstract: The number of hemoglobinopathy patients in North America continues to increase, due to high rates of immigration from countries with high prevalence and improved survival. Recent research has led to evidence-based improvements in acute and chronic care of patients with sickle cell disease and thalassemia. Studies have noted gaps in clinicians’ knowledge about management of hemoglobinopathies, with the result that common presentations, such as sickle vaso-occlusive episodes, are often mismanaged. Hematologists completing training in North America require the knowledge and expertise to manage these medically complex patients. To ascertain the extent of hemoglobinopathy teaching and exposure in Canadian Adult and Pediatric Hematology Training Programs, and to assess the perceived importance of hemoglobinopathy knowledge, we administered an online survey to all Training Program Directors (TPDs), and to all residents who were currently enrolled or who had completed training in the previous year. Surveys were available in English and French. The response rate for TPDs was 92% (22/24). Ninety five percent of PDs felt that hemoglobinopathy learning is “important” or “very important” for hematology trainees in their region. Four programs have a mandatory hemoglobinopathy rotation, 14 programs have mandatory hemoglobinopathy clinic participation, and 17 programs have mandatory hemoglobinopathy lab exposure. Laboratory time ranges widely, from “0-2 hours” to “greater than 20 hours”. All programs covered laboratory aspects of hemoglobinopathy, outpatient care of sickle cell disease and inpatient care of sickle cell disease, and all but one program covered outpatient care of thalassemias. In 1/2 to 2/3 of adult training programs, these topics were covered at only a basic level. All pediatric programs covered outpatient and inpatient care of sickle cell disease “in-depth”, with 90% and 40% of programs covering outpatient thalassemia care and laboratory diagnostics “in-depth”, respectively. All 22 programs had academic half-days with teaching devoted to hemoglobinopathy. Seventy-seven percent of programs had faculty member(s) with an interest in hemoglobinopathy. The response rate for residents was 45% (70/156). The majority of respondents were senior residents, with 88% currently in post-graduate year five, or above. Among residents in adult hematology programs, 61% had completed a rotation or elective with a focus on hemoglobinopathy versus 25% in the pediatric programs. Total numbers of hemoglobinopathy patients seen ranged from “0” to “more than 50”, and laboratory exposure varied from “none” to “in-depth”. Most residents with clinical hemoglobinopathy experience had seen patients with both sickle cell disease and thalassemia major or intermedia. Of residents who responded, 83% felt that hemoglobinopathy knowledge was “important” or “very important” to their future practice. All TPDs and 90% of residents felt that online hemoglobinopathy learning modules could be beneficial for resident learning. There appears to be wide variability in depth and breadth of clinical and laboratory hemoglobinopathy learning in Hematology training programs across Canada. TPDs and residents place high importance on hemoglobinopathy learning, but some centres have small patient numbers, or lack faculty with interest in hemoglobinoapthies. Online learning modules could provide added learning opportunities for residents. Disclosures No relevant conflicts of interest to declare.