American Society Of Hematology Research Articles

Authorship characteristics of hematology and oncology education chapters: A comprehensive analysis

IntroductionAchieving diversity and equity in healthcare, especially within academic and clinical spheres, poses significant challenges. This study aims to evaluate gender representation, geographical diversity among authors, and disclosure of conflicts of interest (COIs) in educational materials published by the American Society of Clinical Oncology (ASCO) and the American Society of Hematology (ASH). Materials and methodsWe conducted a comprehensive cross-sectional analysis covering all volumes of ASCO and ASH educational chapters from 2012 to 2022 and 2000 to 2022, respectively. Author data were extracted from the official websites of ASCO and ASH educational books, focusing on names, affiliations, countries of practice, COIs, and publication titles/subjects. ResultsAnalysis of 2796 articles revealed significant trends in gender representation. Women comprised 44 % of first authors and 38 % of last authors in ASCO educational books, and 39 % of first authors and 39% of last authors in ASH educational books. Notably, there was a marked increase in female first and last authors over time across both ASCO and ASH publications (p < 0.001). Geographical diversity showed disparities, with the majority of authors affiliated with US institutions (72 % of first and last authors). International authors were less represented, with Canada, the UK, and Italy prominent among articles featuring international women authors. A substantial portion of analyzed articles disclosed COIs, mainly research funding, honoraria, and travel expenses. DiscussionOur findings suggest a notable rise in female authorship, potentially reflecting efforts by ASH and ASCO to promote diversity. International authorship remained stable, while COIs were prevalent, primarily involving research funding. Addressing the need for greater international engagement and improving COI reporting quality are crucial to promote inclusivity and transparency in academic publications.

Distinguishing ASH clinical practice guidelines from other forms of ASH clinical advice

AbstractThe American Society of Hematology (ASH) develops a variety of resources that provide guidance to clinicians on the diagnosis and management of blood diseases. These resources include clinical practice guidelines (CPGs) and other forms of clinical advice. Although both ASH CPGs and other forms of clinical advice provide recommendations, they differ with respect to the methods underpinning their development, the principal type of recommendations they offer, their transparency and concordance with published evidence, and the time and resources required for their development. It is crucial that end users be aware of the differences between CPGs and other forms of clinical advice and that producers and publishers of these resources use clear and unambiguous terminology to facilitate their distinction. The objective of this article is to highlight the similarities and differences between ASH CPGs and other forms of ASH clinical advice and discuss the implications of these differences for end users.

Decision theoretical foundations of clinical practice guidelines: an extension of the ASH thrombophilia guidelines

AbstractDecision analysis can play an essential role in informing practice guidelines. The American Society of Hematology (ASH) thrombophilia guidelines have made a significant step forward in demonstrating how decision modeling integrated within Grading of Recommendations Assessment, Developing, and Evaluation (GRADE) methodology can advance the field of guideline development. Although the ASH model was transparent and understandable, it does, however, suffer from certain limitations that may have generated potentially wrong recommendations. That is, the panel considered 2 models separately: after 3 to 6 months of index venous thromboembolism (VTE), the panel compared thrombophilia testing (A) vs discontinuing anticoagulants (B) and testing (A) vs recommending indefinite anticoagulation to all patients (C), instead of considering all relevant options simultaneously (A vs B vs C). Our study aimed to avoid what we refer to as the omitted choice bias by integrating 2 ASH models into a single unifying threshold decision model. We analyzed 6 ASH panel's recommendations related to the testing for thrombophilia in settings of “provoked” vs “unprovoked” VTE and low vs high bleeding risk (total 12 recommendations). Our model disagreed with the ASH guideline panels’ recommendations in 4 of the 12 recommendations we considered. Considering all 3 options simultaneously, our model provided results that would have produced sounder recommendations for patient care. By revisiting the ASH guidelines methodology, we have not only improved the recommendations for thrombophilia but also provided a method that can be easily applied to other clinical problems and promises to improve the current guidelines’ methodology.

Converting IMPROVE bleeding and VTE risk assessment models into a fast-and-frugal decision tree for optimal hospital VTE prophylaxis

AbstractCurrent hospital venous thromboembolism (VTE) prophylaxis for medical patients is characterized by both underuse and overuse. The American Society of Hematology (ASH) has endorsed the use of risk assessment models (RAM) as an approach to individualize VTE prophylaxis by balancing overuse (excessive risk of bleeding) and underuse (risk of avoidable VTE). ASH has endorsed IMPROVE (International Medical Prevention Registry on Venous Thromboembolism) risk assessment models: the only RAM to assess short-term bleeding and VTE risk in acutely ill medical inpatients. ASH, however, notes that no RAMs have been thoroughly analyzed for their effect on patient outcomes. We aimed to validate the IMPROVE models and adapt them into a simple, fast-and-frugal (FFT) decision tree to evaluate the impact of VTE prevention on health outcomes and costs. We used 3 methods: the “best evidence” from ASH guidelines, a “learning health system paradigm” combining guideline and real-world data from the Medical University of South Carolina (MUSC), and a “real-world data” approach based solely on MUSC data retrospectively extracted from electronic records. We found that the most effective VTE prevention strategy used the FFT decision tree based on an IMPROVE VTE score of ≥2 or ≥4 and a bleeding score of <7. This method could prevent 45% of unnecessary treatments, saving ∼$5 million annually for patients such as the MUSC cohort. We recommend integrating IMPROVE models into hospital electronic medical records as a point-of-care tool, thereby enhancing VTE prevention in hospitalized medical patients.

Epidemiology, Treatment Trends, and Outcomes of Multiple Myeloma in the Middle East and Africa: A Systematic Review

Background Globally, multiple myeloma (MM) ranks 24th among the most common cancers. The Middle East and Africa are affected by an increasing trend in MM incidence, owing to several underlying factors. This systematic review aims to assess the epidemiology, patient characteristics, and treatment outcomes associated with MM in selected countries in the Middle East and Africa. Methods An electronic search was performed in the PubMed/MEDLINE database. Abstracts presented at the annual meetings of the American Society of Clinical Oncology, American Society of Hematology, and European Society for Medical Oncology and the GLOBOCAN registry were searched. Qualitative analysis was performed. Results A total of 412 articles were screened, and 14 were selected. The five-year prevalence per 100,000 gathered from country-wise GLOBOCAN data ranged between 155 in Kuwait and 5,625 in North Africa. The identified treatment options were proteasome inhibitors such as bortezomib, drugs such as thalidomide, lenalidomide, dexamethasone, melphalan, and cyclophosphamide, and newer drugs such as daratumumab. Conclusion Improved diagnostic capability has increased the incidence of MM in this region. However, advanced drugs and treatment regimens remain unaffordable in many countries of these regions. Therefore, understanding the trends of the disease and improving healthcare settings are imperative.

ChatGPT's innovative application in blood morphology recognition.

Recently, the rapid advancement in generative artificial intelligence (AI) technology, such as ChatGPT-4, has sparked discussions, particularly in image recognition. Accurate results are critical for hematological diagnosis, particularly for blood morphology identification. Despite advanced hematology analyzers, reliance on professional hematopathologists for manual identification remains in cases of abnormal or rare conditions, a process prone to human subjectivity and potential errors. Consequently, this study aimed to investigate the potential of ChatGPT-4 to assist with blood morphology identification. We conducted a retrospective study using blood images obtained from the American Society of Hematology (ASH). These images comprised a range of normal and abnormal morphologies. Each sample was analyzed by expert technicians (control group) and classified using ChatGPT-4 (test group). Preliminary results showed that ChatGPT-4 could identify normal blood cells with an accuracy of 88%, exceeding the accuracy of identifying abnormal blood cells at a rate of 54%. Regarding identifying abnormal cells, the accuracy of ChatGPT-4 was slightly higher than that of the manual method, which was 49.5%. This study shows that although generative AI shows the potential for blood type identification, it has not yet reached the point where it can replace the professional judgment of medical staff. The results showed that ChatGPT-4 is excellent for identifying red blood cell morphology, particularly inclusion bodies. It can be used as an auxiliary tool for clinical diagnosis. However, the overall recognition accuracy must be further improved. Our study produced innovative results in this field, establishing a foundation for future studies and highlighting the potential of generative AI in aiding blood morphology recognition. Future research should focus on enhancing the effectiveness of AI to improve overall standards of medical care.

Advanced practice providers in hematology: actionable findings from national paired APP and physician surveys

AbstractAdvanced practice providers (APPs) are critical to the hematology workforce. However, there is limited knowledge about APPs in hematology regarding specialty-specific training, scope of practice, challenges and opportunities in APP-physician interactions, and involvement with the American Society of Hematology (ASH). We conducted APP and physician focus groups to elucidate major themes in these areas and used results to inform development of 2 national surveys, 1 for APPs and 1 for physicians who work with APPs. The APP survey was distributed to members of the Advanced Practitioner Society of Hematology and Oncology, and the physician survey was distributed to physician members of ASH. A total of 841 APPs and 1334 physicians completed the surveys. APPs reported most hematology-specific knowledge was obtained via on-the-job training and felt additional APP-focused training would be helpful (as did physicians). Nearly all APPs and physicians agreed that APPs were an integral part of their organizations and that physician-APP collaborations were generally positive. A total of 42.1% of APPs and 29.3% of physicians reported burnout, and >50% of physicians felt that working with APPs had reduced their burnout. Both physicians and APPs reported interest in additional resources including “best practice” guidelines for APP-physician collaboration, APP access to hematology educational resources (both existing and newly developed resources for physicians and trainees), and greater APP integration into national specialty-specific professional organizations including APP-focused sessions at conferences. Professional organizations such as ASH are well positioned to address these areas.

Improving methods of clinical practice guidelines: From guidelines to pathways to fast-and-frugal trees and decision analysis to develop individualised patient care.

Current methods for developing clinical practice guidelines have several limitations: they are characterised by the "black box" operation-a process with defined inputs and outputs but an incomplete understanding of its internal workings; they have "the integration problem"-a lack of framework for explicitly integrating factors such as patient preferences and trade-offs between benefits and harms; they generate one recommendation at a time that typically are not connected in a coherent analytical framework; and they apply to "average" patients, while clinicians and their patients seek advice tailored to individual circumstances. We propose augmenting the current guideline development method by converting evidence-based pathways into fast-and-frugal decision trees (FFTs) and integrating them with generalised decision curve analysis to formulate clear, individualised management recommendations. We illustrate the process by developing recommendations for the management of heparin-induced thrombocytopenia (HIT). We converted evidence-based pathways for HIT, developed by the American Society of Hematology, into an FFT. Here, we consider only thrombotic complications and major bleeding. We leveraged the predictive potential of FFTs to compare the effects of argatroban, bivalirudin, fondaparinux, and direct oral anticoagulants (DOACs) using generalised decision curve analysis. We found that DOACs were superior to other treatments if the FFT-predicted probability of HIT exceeded 3%. The proposed analytical framework connects guidelines, pathways, FFTs, and decision analysis, offering risk-tailored personalised recommendations and addressing current guideline development critiques.

A GLOBAL CONGRESS DIGEST ON TARGETED THERAPIES IN B-CELL MALIGNANCIES. Report from the American Society of Hematology (ASH) Annual Meeting, December 9–12, 2023

A GLOBAL CONGRESS DIGEST ON TARGETED THERAPIES IN B-CELL MALIGNANCIES. Report from the American Society of Hematology (ASH) Annual Meeting, December 9–12, 2023

Anticoagulation management in patients tested for heparin-induced thrombocytopenia in the cardiothoracic intensive care unit diverges from expert guidelines

Abstract Heparin-induced thrombocytopenia (HIT) is a rare, life-threatening complication in patients receiving heparin products. Clinical scoring tools, such as the ‘4T’ score, aim to help identify patients at risk for HIT and are recommended by expert guidelines. For example, the American Society of Hematology (ASH) recommends that patients with an intermediate or high-risk 4T score are presumptively treated for HIT by withdrawing heparin and starting an alternative anticoagulant. At our institution, laboratory HIT testing involves an in-house latex immunoassay (LIA) that, if positive, reflexes to a send-out serotonin release assay (SRA) at the Blood Center of Wisconsin. This confirmation may take several days to result, underscoring the importance of presumptive treatment. Anecdotally, we have observed that clinicians have expressed reservations about the use of the 4T score in the cardiothoracic intensive care unit (CTICU). These reservations may lead to increased HIT testing in patients with low 4T scores and delays in the initiation of alternative anticoagulants. We set out to objectively determine if clinical practice in the CTICU is aligned with ASH guidelines. To do so, we used anticoagulant usage as a proxy for medical decisions made at the time of order for HIT laboratory testing. Data was extracted from the electronic medical records of all patients who were admitted to the CTICU between 5/2018 and 7/2022 and administered a heparin product (n = 1,602). Patients that were not tested for HIT (n = 1,449) were excluded. The remaining patients’ (n = 153) medication record timings were normalized such that the time of their first LIA was set to zero to allow for relative comparisons. 25 (16%) of the LIAs were positive, of which 5 (20%) were confirmed by SRA. Of the 153 patients, 136 (89%) received heparin within 24 hours prior to LIA order, while 6 (4%) were already on alternative anticoagulation (bivalirudin). Of the patients on heparin prior to LIA, 18 (13%) were switched to bivalirudin upon LIA order, 66 (49%) had heparin discontinued without an alternative, and 52 (39%) were continued on heparin. Our results suggest that the prevalence of HIT in this cohort is 3.3% by SRA, much lower than the expected pretest probability estimated for intermediate- and high-risk 4T scores in published meta-analyses. In addition, the observed anticoagulation practices varied widely and diverged from ASH guidelines, where only 17% of patients were on alternative anticoagulation when the testing was ordered. Future work will investigate these patterns across LIA positivity and 4T scores while attempting to address the clinical outcomes of these treatment decisions.

Comparison of Alloimmunization in Pregnant People with Sickle Cell Disease Receiving Chronic Versus on-Demand Transfusions: A Multinational Study

Introduction Despite exceptional maternal morbidity and mortality risk, people with sickle cell disease (SCD) lack firm indications for chronic transfusion therapy (CTT) during pregnancy. Alloimmunization may cause hemolytic transfusion reactions and can limit the safety of future blood transfusions; thus it is a rationale for restricting CTT during pregnancy. Little data quantifies this risk. The 2020 American Society of Hematology (ASH) Guidelines for SCD TransfusionSupport recommend CTT in some pregnancies, but adoption in clinical practice is unknown. This study's purpose is to use a large two-center SCD pregnancy cohort to describe alloimmunization rates in SCD pregnancies treated with CTT vs on-demand transfusion (ODT) and to determine the fraction of SCD pregnancies meeting the ASH Guideline to initiate CTT in pregnancy. Methods We reviewed SCD pregnancies delivered at Mt. Sinai Hospital, Toronto (1990-2017) and Johns Hopkins Hospital (2000-2021). We collected data on transfusions and SCD complications before and during pregnancy, delivery, and fetal outcomes. Analyses classified subjects and pregnancies as receiving CTT or ODT. We defined CTT as pregnancies treated with scheduled, prophylactic transfusions; ODT as pregnancies transfused as-needed, including no transfusions. Sinai routinely matched transfusions for Rh and K antigens while Hopkins matched Rh only. Both centers provided extended matching if an alloantibody was detected. The first analysis included singleton pregnancies to primigravida subjects. We compared new alloantibody development, SCD complications, and pregnancy outcomes in CTT vs. ODT groups and in genotype stratified groups. We used Chi-squared and Wilcoxon rank-sum tests for categorical and continuous variables; p &amp;lt; .05 was significant. The second analysis included all cohort pregnancies and identified which met criteria for CTT per ASH Transfusion Guidelines which advise CTT for (A) severe SCD complications before or during pregnancy here defined by acute chest syndrome (ACS) or pain requiring acute care in the year before or during pregnancy, any history of venous thromboembolism (VTE), stroke, or multi-organ failure or (B) features of high-risk pregnancy, defined by multiple gestation, pre-eclampsia, gestational hypertension, cardiac comorbidities, or preterm labor history. Results Among 145singleton, primigravida pregnancies, more received ODT than CTT (119 ODT vs 26 CTT). Among ODT subjects 46/119 received at least one transfusion during pregnancy. CTT subjects had more severe SCD than ODT subjects before pregnancy (Table 1). During pregnancy, SCD severity did not differ (Table 2). Before pregnancy, 18 subjects were alloimmunized and did not differ by treatment group (6/26 CTT vs 12/119 ODT, p=0.07). During pregnancy, six subjects developed an alloantibody and did not differ by treatment group (1/26 CTT vs 5/119 ODT, p=0.93). Half (3/6) had a history of alloimmunization before pregnancy (1 CTT vs 2 ODT, p=0.27) and three did not (0 CTT vs 3 ODT, p=0.27). All subjects with new antibodies during pregnancy and historic alloimmunization developed anti-K antibodies (1 CTT, 2 ODT) at both sites. Those without alloimmunization history developed anti-Jkantibodies (3 ODT) at Sinai. In the secondary analysis, we included 299 pregnancies to 203 subjects. Among them, 249 pregnancies (83%) met at least one ASH Guideline criteria for initiating CTT. This included all CTT pregnancies (61/61, 39 subjects) and 79% of ODT pregnancies (188/238, 164 subjects), 46% of which received at least one transfusion during pregnancy (86/188). Conclusions In this SCD pregnancy cohort, alloimmunization rates were low and did not differ between those treated with CTT versus ODT. As alloimmunization events were inconsistent with institutional matching practices, new antibody development may be attributable to transfusions from outside hospitals or pregnancy-associated alloimmunization. Antigen matching per ASH Transfusion Guidelines avoids C, E, K and Jk alloimmunization. Scheduled transfusions may reduce emergency transfusion which increases alloimmunization risk. Finally, all CTT and 79% of ODT pregnancies met ASH Guideline criteria for CTT in pregnancy, however the cohort predates ASH Guideline publication. Guideline adherence may lead to increased use of CTT during pregnancy. More discriminating tools are needed to inform CTT use in SCD pregnancy.

Utilization of Pharmacologic and Non-Pharmacologic Therapies for Pain in Sickle Cell Disease: A Cross-Sectional Study

Background: The sickling deformity of red blood cells in sickle cell disease (SCD) results in multisystem sequelae, including severe, acute pain from vaso-occlusive crises (VOCs) and chronic pain from central sensitization. Pain is the main cause of poor quality of life and hospital admissions among patients with SCD. While opioid therapy is an important component of treatment for acute SCD pain, it can be complicated by side effects and toxicities. In contrast, chronic SCD pain is best managed with non-pharmacologic therapies. A multimodal, multidisciplinary approach to pain management that promotes non-pharmacologic therapies can improve the quality of care for patients with SCD by addressing biopsychosocial components of the pain experience and is recommended by the American Society of Hematology (ASH). This study examines current usage of pharmacologic and non-pharmacologic therapies among Adolescents and Young Adults (AYAs) with SCD receiving care at our institution. Methods: The electronic medical record and Sickle Cell Knowledgebase, a customized data visualization platform unique to our institution, were utilized to conduct a retrospective chart review of AYAs, ages 13-21 years of age, with SCD from 2016-2021. Data collected included demographic information, diagnosis of chronic pain, emergency department (ED) visits and inpatient admissions for VOCs, as well as pharmacologic and non-pharmacologic therapies utilized in the ED, inpatient setting, and, for patients with chronic pain, in the outpatient setting. Results: The cohort included 90 AYAs with SCD (73% were 13-17 years old). The most common SCD genotypes were HbSS (n=47, 52%) and HbSC (n=32, 36%). The majority were female (n=53, 49%), Black (n=85, 94%), and non-Hispanic (n=86, 96%). There were 95 ED visits for VOC, where the patient was subsequently discharged home, and 246 admissions for VOC during the study period. There was a high frequency of opioid interventions for VOCs during the 95 extracted ED visits (81.8% in 2016, 91.7% in 2021). During VOC admissions, there was consistent use of opioids in 100% of admissions from 2016-2021 with increasing utilization of patient-controlled analgesia (7.7% in 2016, 45.1% in 2021) and subanesthetic ketamine (0% in 2016, 18.3% in 2021) each year during the study period. Compared to pharmacologic measures, non-pharmacologic therapies (i.e., healing touch, massage, art therapy, child life, music therapy, occupational therapy, physical therapy, psychology) were less utilized during VOC admissions. While healing touch and child life therapy were ordered during approximately 85% of VOC admissions, they occurred &amp;lt;50% of the time. All other integrative therapies were ordered between 5-55% of admissions each year and occurred &amp;lt;50% of the time. There was no correlation between length of hospital stay and use of integrative therapies. Seven patients with a diagnosis of chronic pain were identified. All 7 received non-pharmacologic therapies in the outpatient setting, including cognitive behavioral therapy, guided imagery, and psychology consultation. Six received either a gabapentinoid, serotonin and norepinephrine reuptake inhibitor (SNRI), or tricyclic antidepressant (TCA). Conclusion: Per the ASH SCD guidelines, non-pharmacologic therapies are recommended for SCD-related pain. In our cohort, we found that non-pharmacologic therapies occurred in &amp;lt;50% of VOC admissions and were underutilized for SCD-related pain in AYAs when compared to pharmacologic therapies at our institution. Though we speculate that healing touch and child life were frequently ordered as a default within our admission order set, utilization rates were still low. To better understand barriers to non-pharmacologic therapies in SCD, we are conducting qualitative interviews of patients, caregivers, and healthcare providers using the Consolidated Framework for Implementation Research (CFIR) as a theoretical model. Understanding barriers to the use of non-pharmacologic therapies will be essential to maximizing their implementation and hence maximizing pain control, improving quality of life, and increasing self-efficacy.

Improving the Outpatient Pain Management Plan for Patients with Sickle Cell Disease with Electronic Medical Record-Based Pain Action Plans

Background: Patients with sickle cell disease (SCD) experience recurrent vaso-occlusive crises (VOC) as a primary manifestation of their illness. The American Society of Hematology (ASH) best practice guidelines recommend that individuals with SCD have individualized care plans to effectively begin pain management at home prior to presenting to the emergency room. A needs assessment of the comprehensive sickle cell program at Rady Children's Hospital San Diego (RCHSD) identified the need for a standardized approach for the provision of Pain Action Plans (PAP). In 2022, an outpatient PAP Quality Improvement (QI) project was initiated at RCHSD with the global aim to improve outpatient pain management and quality of life for patients with SCD. SMART Aim: Within 6 months (January-June 2023), to increase the proportion of patients with SCD receiving a PAP during a comprehensive clinic visit from 0 to 50%. Methods: The QI project was conducted by an interprofessional team with clinical, QI, and information technology expertise. An initial approach utilizing the Med Action Plan function in EPIC had technical challenges and was not implemented. We identified an existing Epic Asthma Action Plan which could be adapted to a SCD PAP. Meetings with clinical informaticists, pulmonology (consultants), and hematology teams informed the QI tools (process mapping, key driver and Ishikawa diagrams) that we used to design our PDSA cycles. The PAPs were modeled after the existing Asthma Action Plan, with green, yellow, and red zones to indicate different levels of pain management. Patients were given laminated Youth Acute Pain Functional Ability Questionnaire (YAPFAQ) and a comfort measures sheet to complete prior to their visit with the provider to inform the PAP which included pain medication details and supportive care measures for each zone. PAPs were created within the clinic note at comprehensive clinic visits and then provided to the family as a printed letter in person and via MyChart (if activated). Our outcome measure was the percentage of patients who were provided a PAP at their SCD comprehensive clinic visit. Process measures included the percentage of patients who had documentation in the PAP of the YAPFAQ and comfort measures, percentage of patients who had a PAP routed to patient via MyChart, percentage of patients who confirmed receipt of their PAP, percentage of patients who had used their PAP by parental report after one week, and percentage of patients who had used their PAP after 3 months per Epic documentation. Balancing measures were the perceived burden of patient care/documentation for the PAP to be evaluated with pre and post surveys among providers. Results: Interventions were evaluated using PDSA cycles. PDSA Cycle 1 (January-March 2023) included development of the SCD PAP by adapting the existing Asthma Action Plan to a SCD PAP. This included the creation of medication templates, integrating comfort measures and pain triggers, creating EPIC smart phrases to document the YAPFAQ. We educated providers on the SCD PAP and documentation process and worked with the interdisciplinary team including case managers, nurses, child life specialists, and psychologist to incorporate YAPFAQ and comfort measures into the comprehensive clinic visit. PDSA Cycle 2 (April-June 2023) included additional education, training, and targeted e-mail reminders to hematology attendings. From May 2023 to July 2023, 94% percent (13/14) of patients seen at a comprehensive clinic visit received a PAP. One patient had the PAP created but did not receive the printed letter due to time constraints for family. Feedback from families indicated that they felt the PAP was a valuable tool to have at home during VOC, however none had yet utilized it in the week since they were seen in clinic. Early provider feedback has indicated that this functionality is easy to use and efficient during the comprehensive clinic visit. Conclusion: The adaptation of the Asthma Action Plan to the SCD PAP allowed for successful implementation of PAPs for our patients with SCD. Subsequent PDSA cycles will focus on optimizing implementation in the clinic and utilization for pain events. We will evaluate the clinical impact of the PAPs on pain management outcomes.

Patient, Caregiver, and Healthcare Provider Perspectives on Pharmacologic and Non-Pharmacologic Therapies for Pain in Sickle Cell Disease

Background: Pain is the main cause of poor quality of life among patients with sickle cell disease (SCD). While opioid therapy is the mainstay of treatment for acute SCD pain, it can be complicated by side effects and toxicities. A multimodal, multidisciplinary approach to pain management that promotes non-pharmacologic therapies can improve the quality of care for patients with SCD by addressing biopsychosocial components of the pain experience. Guided by the Consolidated Framework for Implementation Research (CFIR), this study utilized qualitative interviews with patients, caregivers, and healthcare providers at our institution to assess barriers to the use of non-pharmacologic and pharmacologic therapies for pain in SCD. Methods: Semi-structured qualitative interviews were conducted with adolescents and young adults (AYAs; ages 13-21) with SCD, caregivers of AYAs with SCD, and healthcare providers at our institution. AYAs had either a documented history of chronic pain and/or ≥1 admission/year for vaso-occlusive crises (VOCs) for at least one year from 2016-2022. After informed assent and/or consent were obtained, individual semi-structured interviews were conducted. Open-ended interview questions explored existing knowledge, perceptions, and barriers to pharmacologic and non-pharmacologic therapies for pain in SCD. Interviews proceeded until no new themes emerged in each group (i.e., thematic saturation). Interviews were analyzed using descriptive content analysis facilitated by Dedoose software. The CFIR and prior research informed a preliminary codebook, which was revised as new themes emerged. The coders independently coded transcripts and then met to discuss and resolve any discrepancies in coding. Results: Demographics: Eighteen AYAs, 17 caregivers, and 22 healthcare providers were interviewed. Of the AYAs, 61% were female, mean age was 17 years, and the most common SCD genotype was HgbSS (56%). Of the caregivers, 88% were mothers, with a mean age of 43 years. There were 15 AYA/caregiver dyads who participated. The following healthcare providers who care for patients with SCD were interviewed: physicians (31%), nurse practitioners (14%), nurses (14%), child life specialists (14%), psychologists (9%), art therapists (4.5%), healing touch providers (4.5%), physical therapists (4.5%), and social work (4.5%). Themes: Barriers to the use of non-pharmacologic therapies for pain management in SCD can broadly be grouped into two major themes: lack of knowledge about options and lack of access to non-pharmacologic options. Regarding lack of knowledge, most AYAs and caregivers endorsed a lack of knowledge about specific non-pharmacologic therapies (e.g., yoga therapy, healing touch, acupuncture), including their benefits, risks, and their abilities to reduce pain. Like AYAs and caregivers, many healthcare providers had limited knowledge about specific non-pharmacologic therapies and the evidence in support of their usage. Regarding lack of access to specific options, the majority of participants questioned the ability of patients to access non-pharmacologic options for pain management including availability of options and cost of access. Additional themes included a desire for more education about pain and pain management options. AYAs and caregivers were particularly interested in more information about yoga. Additionally, AYAs and caregivers were interested in education early in life before pain episodes occurred. Conclusions: Emerging themes among all groups include an interest in non-pharmacologic therapies for pain in SCD, but with limited knowledge on benefits, risks, options, and access to these therapies. As the American Society of Hematology (ASH) guidelines recommend non-pharmacologic therapies for sickle cell pain, it is crucial to implement these therapies into the management of pain in SCD. Education about different options paired with implementation options for ways to incorporate non-pharmacologic therapies is necessary to optimize pain control and improve quality of life. A particular focus on yoga therapy, with availability of a yoga therapist in medical settings, and organized yoga education events specific for SCD may be beneficial to engage individuals in yoga therapy with a trained yoga-therapist. As a next step, evaluation of these potential implementation strategies will occur within our health system.

Clinical Factors but Not Somatic Mutations Predict for Survival in Patients with Myelofibrosis Undergoing Allogeneic Hematopoietic Cell Transplant: Analysis of the North American Myelofibrosis Transplant Outcome (NAMTO) Study

Introduction: Myelofibrosis (MF) is a clonal hematologic malignancy characterized by constitutive JAK-STAT activation and aberrant cytokine signaling. Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only potentially curative therapy in MF. The contribution of disease-, patient- and donor-related factors to allo-HCT outcomes remains to be fully elucidated, as well as the presence of somatic mutations in genes such as ASXL1, EZH2, SRSF2, U2AF1 and IDH1/2 which are associated with worse prognosis in MF patients (pts). In this large multi- center retrospective analysis, we aimed to study the impact of clinical and molecular mutations on transplant outcomes. Methods: This analysis including 498 pts from 11 centers in North America and Canada. Univariate proportional-hazard Cox regression analysis stratified by center was used to assess the association of patient, transplant, and disease characteristics on overall survival (OS). Baseline patient demographic data and disease characteristics were selected as covariates in the multivariate analysis. Results: Pts transplanted between 2002-2021 were included in this analysis. Baseline and transplant characteristics are summarized in table 1. The 1- and 2-year OS was 77% (95% CI; 73-81) and 70% (95% CI; 66-74) and non-relapse mortality (NRM) 19% (95% CI: 17-21) and 23% (95% CI: 19-27), respectively. The cumulative incidence (CMI) of relapse at 1- and 2-years was 12% (95% CI; 10-14) and 16% (95% CI; 12-20). The CMI of acute graft versus host disease (aGVHD) grade II-IV was 31% (95% CI; 27-35) at 3 months and 42% (95% CI; 38-46) at 1-year post-transplant and grade was III-IV 13% (95% CI; 11-15) and 18% (95% CI; 14-22), respectively. The CMI of neutrophil engraftment at 1 and 3 months was 90% (95% CI: 87-93) and 97% (95% CI: 95-95) and for platelets 55% (95% CI: 50-59) and 80% (95% CI: 76-83). Univariate analysis included pts (age and gender), transplant (donor type and conditioning regimen intensity) and disease characteristics (DIPSS, mutations, cytogenetics (CG), blood counts, and spleen size). Hemoglobin &amp;gt; 10 g/dL (HR .5, 95% CI .34 -.73 p=3 x 10 -4) and platelets &amp;gt;50× 10 9/L (HR .59, 95% CI .42-.81, p=.0013) prior to transplant were associated with improved OS. High risk DIPSS was associated with decreased OS (p=0.0002). Mutations in ASXL1, EZH2, IDH1/2, U2AF1 and SRSF2 were not associated with decreased OS in this analysis (Figure 1). However, mutations in ZRSR2 were associated with inferior OS (HR 2.07, 95% CI 1.08-3.95, p=.0252). Lastly, JAK2 which had the most frequent mutations was not associated with OS (HR .0.93, 95% CI .65-1.31). There was no association between the CG risk groups and OS. Splenomegaly, measured radiographically, had no impact on OS but was strongly associated with engraftment (better engraftment defined as HR&amp;gt;1). For platelets, spleen size of 15.6-18.9 cm HR of 0.69 (95% CI .47-1, p=.0489) and size &amp;gt;18.9-22.5 cm HR of 0.48 ( 95% CI .33-.7, p=1x10^-4). For neutrophils, spleen size &amp;gt;19.9-22.5 cm had a HR of 0.68, (95% CI .48-.96, p=.0268) and size&amp;gt;22.5 cm had a HR of 0.65 (95% CI .46-.91, p=.0114). Mismatched unrelated (MMURD) and haplo identical donors had no impact on survival but were associated with delayed platelet engraftment; MMURD (HR .67, 95% CI .47-.96, p=.0298) and haploidentical donors (HR .56, 95% CI .39-.8, p=.0017). In a multivariate analysis adjusted for age, gender, highest DIPSS, donor type and conditioning regimen, platelets &amp;gt; 50× 10 9/L (HR .61, 95% CI .44-.87, p=.0053) hemoglobin &amp;gt;10 g/dL (HR .6, 95% CI .4-.9, p=.0244) and lower DIPSS at the time of transplant were associated with improved OS. Conclusions: In this large multicenter analysis only clinical variables; hemoglobin and platelets, were found to be associated with OS after allo-HCT in MF patients. Somatic mutations associated with poor prognosis were not associated with OS suggesting that transplant can overcome their negative impact. Splenomegaly was associated with delayed engraftment but not OS. Interestingly, using alternative donors (MMURD and haplo identical) didn't have a negative effect on OS, possibly reflecting the use of post-transplant cyclophosphamide for GVHD prophylaxis in recent years. These results highlight the importance of biologic factors in the prognostication of outcomes in MF pts undergoing allo-HCT independent of somatic mutations. Supported by the American Society of Hematology (ASH) and MPN Research Foundation

Rates and Predictors of Prophylaxis in Women with Von Willebrand Disease and Heavy Menstrual Bleeding

Background: Women with von Willebrand disease (vWD) suffer from heavy menstrual bleeding (HMB) often complicated by iron deficiency anemia (IDA) and reduced quality of life. Despite the American Society of Hematology (ASH) recommendations for long-term prophylaxis in patients with severe frequent bleeds, prophylaxis remains under-utilized in women with severe HMB. Given the scarcity of data on management of gynecological bleeding, it is critical to examine our practice patterns and identify factors associated with prophylaxis use. Aims: 1) To evaluate the management and outcomes of gynecological bleeding in vWD, including rates of desmopressin (DDAVP) and vWF prophylaxis for HMB and predictors of their use. 2) To examine the association between prophylaxis and severe HMB. Methods: This retrospective cohort study included women ≥18 years diagnosed with vWD in the Northern Alberta Bleeding Disorders Program. We assessed the rates of HMB, severe HMB and IDA, along with their management strategies. Prophylaxis rates with DDAVP and vWF concentrates, as well as predictors of their use, were examined. Severe HMB was defined as HMB requiring Emergency Department (ED) visits, hospitalizations, blood transfusions, or surgical management (dilation &amp; curettage [D&amp;C], endometrial ablation or hysterectomy). IDA was defined as ferritin &amp;lt;30 mcg/L and hemoglobin &amp;lt;120 g/L. Logistic regression was used to examine factors associated with severe HMB. Variables with P-value &amp;lt;0.20 on univariate regression were included in multivariable regression. Results: 168 women were evaluated with a median age of vWD diagnosis of 27 years (IQR 18-38): 140 (81%) type 1, 23 (13%) type 2, and 5 (3%) type 3 vWD. Among those with type 1 vWD, 43 (31%) had baseline vWF levels &amp;lt;0.30 IU/ml, 94 (67%) had vWF levels of 0.30-0.49 IU/ml, and 3 (2%) had missing values. DDAVP response was assessed in 124/140 (89%) type 1 vWD and 13/23 (57%) type 2 vWD. There were 145 (86%) women with HMB, managed most commonly by tranexamic acid (TXA) (112; 77%), followed by hormonal therapy (73; 50%), subcutaneous DDAVP (40; 28%), and levonorgestrel intrauterine system (39; 26%). vWF prophylaxis was used in only 11 (8%) women. Surgical procedures for HMB were common including hysterectomy (28; 19%), endometrial ablation (15; 10%) and D&amp;C (15; 10%). Over a quarter (39; 27%) received iron infusions. Of the 65 (45%) women with a history of IDA, 6 (9%) had persistent IDA &amp;gt;5 years, 6 (9%) had IDA lasting 2-5 years and 53 (65%) had IDA corrected within 2 years. Prophylaxis rates did not differ between the 68 (40%) women with severe HMB and the 77 (53%) with non-severe HMB, with comparable rates of VWF use (9% vs 6%, P=0.60). Compared with women who never received prophylaxis, those who received DDAVP or vWF prophylaxis were more likely to have received TXA (93% vs 70%, P=0.003), iron infusions (43% vs 19%, P=0.004) and to have been diagnosed before 2000 (22% vs 7%, P=0.03) (Table 1). Though non-significant, a higher proportion of type 3 vWD (9% vs 1%, P=0.06) and higher ISTH-BAT (median 8 vs 7, P=0.07) were observed in prophylaxis recipients. On multivariable logistic regression, time from first bleeding symptom to diagnosis (adjusted odds ratio [aOR] 1.04, 95% CI 1.01-1.07) and prophylactic DDAVP use (aOR 2.4, 95% 1.01-5.6) were associated with severe HMB. There was a non-significant trend towards lower odds of severe HMB in patients diagnosed in 2000-2010 and 2011-2021 as compared to pre-2000 (aOR 0.3, 95% 0.1-1.0). Diagnosis before age 18, vWD type and baseline vWF activity were not associated with severe HMB. Conclusion: Women with vWD experience high rates of HMB and its associated complications. In our study, there was a relatively high uptake of DDAVP prophylaxis, however vWF prophylaxis was under-utilized even in those with severe HMB. We failed to demonstrate an impact of either prophylactic therapy on severe HMB, though this may be due to confounding by indication. There was a significant association between prophylactic DDAVP and vWF with other quality of care indicators including TXA and iron infusions. It is unclear if this association is related to practice patterns or patient factors such as access to care or preference for early definitive treatment. Overall, our findings highlight a need to further understand the barriers to prophylaxis use and to consider earlier prophylaxis for severe HMB to decrease bleeding complications and the need for resource-intensive therapies.

Comprehensive Analysis of Structural and Social Determinants of Health Leading to Delays in Seeking Hematologic Care: Survey of an Underserved Population with Hematologic Malignancies

Background: Disparities in outcomes based on age, race, and socioeconomic status are well-established among patients with hematologic malignancies. Timely access to health care is essential for successful treatment of aggressive hematologic malignancies. Delays in receiving treatment have been linked to worse cancer outcomes in solid tumors and is presumed to lead to worse outcomes in hematologic malignancies. Memphis, owing to its geography, draws patients from Tennessee, Arkansas, and Mississippi for complex medical care. Patients at our institution frequently belong to underserved communities, including rural, impoverished, underinsured, and racial minority populations. In this exploratory study, we sought to characterize the potential structural and social barriers that patients in an underserved population with hematologic malignancies may face accessing oncologic care around the time of their cancer diagnosis. Methods: A cross-sectional survey was conducted to better understand potential barriers to accessing hematologic care in the greater Memphis area. The survey was developed through a review of existing literature on this topic (i.e., Anderson's conceptual model for healthcare utilization), as well as from the investigators' clinical experience treating cancer patients. Several components of social determinants of health (SDOH), including psychosocial, economic, health literacy, behavioral, health care perceptions, cultural, structural, environmental, clinical, and chronic stress domains, were queried in this 56-item survey. Most items were presented as closed-ended statements on a Likert scale. Response categories for analyses were collapsed into two levels (eg, “agree” for “somewhat” or “strongly”; “concerned” for “somewhat” or “very”). Descriptive statistics, including percentages, means, medians, and ranges, were used to characterize the sample. Results: A total of 41 out of 46 consented patients completed the survey (response rate: 89.1%). The median age of respondents was 56.3 years (Table 1). Most had lymphoma (48.8%), followed by acute myeloid leukemia (17.1%) and multiple myeloma (12.2%). The majority of respondents were male (53.7%) and Black or African American (46.3%). Over half of the sample reported an annual income of less than $25,000 (57.1%) and nearly a third were uninsured at the time of their cancer diagnosis (32.5%). Approximately 44% of respondents believed that medical attention to their cancer symptoms was delayed prior to their cancer diagnosis by a doctor. Of this subset, the majority attributed the delay to economic factors (64%), followed by health literacy (58%), structural (51%), healthcare perceptions (47%), behavioral (45%), psychosocial (45%), chronic stress (43%), cultural (15%) and clinical (11%) reasons (Table 2). Conclusions and Implications: To our knowledge, this is the first survey study to investigate the factors from a patient's perspective that contributed to delays in seeking care for hematologic malignancies. This pilot study establishes the feasibility of approaching an extremely underserved population about sharing their experiences accessing medical care around the time of their cancer diagnosis as well as participating in research. Along with already well-established economic, health literacy, psychosocial, and structural barriers, respondents endorsed that health care perceptions and chronic stress contributed almost equally to delays in seeking care. Cultural and clinical barriers contributed the least. Our study findings are limited by a skewed patient selection toward those who survived initial hospitalization and treatment and is not inclusive of the sickest patients in our patient population who experienced neglected cancer symptoms. A mixed-methods, focus-group based study is planned as the next step to substantiate these findings and allow us to gain a deeper understanding into the social disparities that most heavily impact this underserved population. Acknowledgement of Funding: This research was supported by the American Society of Hematology through the ASH HONORS Award.

Sickle Cell Disease Management Practices across Nigeria: A Cross-Sectional Analysis

Introduction Of 300,000 children born with sickle cell disease (SCD) in the world, approximately 75% of these are born in Sub-Saharan Africa. Owing to the frequent painful vaso-occlusive and hemolytic episodes associated with this disease, irreversible multi-organ damage and premature mortality are common. For instance, in Nigeria, 490 deaths per 1000 births among children under 5 have been attributed to SCD; this is four times higher compared to mortality in children born without SCD. On the other hand, those with SCD who survive beyond childhood are faced with an estimated life expectancy of 21 years. To address these challenges, guidelines for SCD management were developed by the Nigerian Federal Health Ministry, National Heart, Lung, and Blood Institute (NHLBI), and the American Society of Hematology but their dissemination and implementation has been difficult. To better understand current management practices, we present a preliminary, descriptive analysis of hydroxyurea and blood transfusion practices for sickle cell disease management across Nigeria. Methods Using a cross-sectional design, we collected demographic and practice-related information from eligible clinicians that provide SCD care in Nigeria. The “SCD Knowledge, Attitudes, and Practices - Nigeria” survey was disseminated to pediatric and adult consultant physicians, resident doctors, and nurses through their respective professional communication platforms. SCD-related practices questions were based on the NHLBI recommendations for SCD management which informed the Nigerian Federal Ministry's National SCD Guideline. A 5-point Likert scale was used to answer each question on hydroxyurea use and blood transfusion. Descriptive analyses of current practices were used to characterize these results and bivariate analyses were conducted using Chi-square or Fisher's test as appropriate. Data analysis was performed using SAS 9.4 (SAS Institute; Cary, NC). Ethical approval was obtained from Duke University Institutional Review Board and the University of Nigeria, College of Medicine Health Research Ethics Committee. Results Analysis of SCD-related practices from the first 73 participants who have completed the survey, revealed most respondents to be female (62%), between 35-65 years old (77%), and adult hematologists or nurses (37% and 40% respectively). This group of clinicians provide care mainly to adults (47%), but 45% admitted providing care to both adults and children. Nearly half (45%) of this group provides care for 0-5 individuals with SCD weekly and 57 participants (78%) work in tertiary-level hospitals. Only 22 of those working in tertiary hospitals had a comprehensive SCD center in their hospital compared to those without an SCD center (39% vs. 61%, p=0.0148). SCD experts were also found in tertiary-level hospitals (75% vs. 25%, p&amp;lt;0.0001). General hematologist expertise was also common in tertiary care (88% vs. 12%, p=0.2424). Figures 1 and 2 report HU and blood transfusion practices. Although 73% confirmed hydroxyurea (HU) prescribing and 90% endorsed the use of simple blood transfusions, HU and blood transfusion practices varied greatly. Respondents indicated most educated patients about HU (frequently/always = 74%) and started HU for patients with &amp;gt;3 VOCs in past year (frequently/always = 62%), however, only 31% frequently/always begin at age 9 months (Figure 1). Most respondents reported prophylactic blood transfusions to reduce HbS below 30% (frequently/always = 71%) and 73% frequently/always performed transfusions for acute SCD complications, yet, 60% indicated they never/rarely match for RBC antigens. Conclusion The data highlights SCD-related expertise and specialty care are found more in tertiary-level hospitals. HU practices described may be attributed to the more conservative approach suggested by the Nigerian SCD Management Guideline compared to the NHLBI recommendations, however there is an important opportunity to expand HU prescribing. Blood transfusion, which has historically been considered difficult in this differently resourced setting, was common. However, chelation, leukoreduction/white blood cell filtration, and red blood cell antigen testing were not common. These preliminary findings represent an opportunity for a larger study and future studies to investigate strategies to increase uptake of existing SCD management recommendations.

Systematic Literature Review and Meta-Analysis of Comparative Clinical Evidence Investigating Daratumumab, Lenalidomide, and Dexamethasone (DRd) Versus Bortezomib, Lenalidomide, and Dexamethasone (VRd) As First-Line Treatment for Transplant-Ineligible Newly Diagnosed Multiple Myeloma

Background: Daratumumab in combination with lenalidomide and dexamethasone (DRd) and bortezomib in combination with lenalidomide and dexamethasone (VRd) are currently the only guideline-recommended preferred regimens for primary treatment of transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). The lack of direct head-to-head trials comparing these two preferred regimens makes it difficult for the treating physicians to select optimal frontline treatment for TIE NDMM patients. A number of network meta-analyses comparing the existing therapies in this patient population have been published; however, these studies have certain limitations such as not sufficiently accounting for heterogeneity among trials (MAIA trial included TIE patients only while SWOG S0777 had a mix of TIE and transplant not intended patients), variable duration of follow-up, inclusion of treatments not used in routine clinical practice in the US, and use of aggregate level data from the pivotal trials. Therefore, the current systematic literature review and meta-analysis (MA) aims to identify and aggregate clinical evidence specifically comparing DRd versus VRd as first-line (1L) treatment for TIE patients with NDMM across a wider evidence base, including indirect treatment comparisons and real-world evidence studies. Methods: The protocol was developed in alignment with the PRISMA for systematic review protocols (PRISMA-P) statement. The Population, Intervention, Comparator, Outcome, Study design (PICOS) framework was used to develop the search strategy and structure the reporting of the eligibility criteria. The search strategy was developed by a medical information specialist and peer reviewed. Ovid MEDLINE ®, Embase, and the Cochrane Library databases were searched from January 2019 to June 2023 along with key congresses (International Myeloma Society, American Society of Hematology, European Hematology Association, American Society of Clinical Oncology) from January 2018 to June 2023. These dates were implemented to identify recent literature and to align with the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approvals of DRd for TIE NDMM. Study eligibility was assessed according to pre-specified criteria. Randomized clinical trials (RCTs) and adequately adjusted, non-randomized comparative studies comparing DRd versus VRd for treatment of adult TIE patients with NDMM were identified for inclusion. The primary outcome of interest was progression-free survival (PFS). Risk of bias was assessed using the National Institute for Health and Care Excellence (NICE) checklist. The feasibility of conducting a MA of the included studies was assessed. A frequentist approach was conducted for the MA considering the unit of analysis, varying treatment effects, and risk of bias. The study protocol is available on PROSPERO (CRD42023435119). Results: Of 863 records screened, 4 were included (1 publication and 3 conference abstracts), representing 3 unique studies. Two studies were indirect treatment comparisons and 1 was a retrospective chart review. In each study, TIE NDMM patients treated with DRd had a significantly lower risk of progression/death compared to those treated with VRd (Table 1). After qualitatively reviewing the evidence base and assessing between-trial clinical and methodological heterogeneity, it was considered feasible to conduct a MA of PFS including all 3 identified studies. Results from the MA (Figure 1) suggest that patients treated with DRd had a lower risk of progression/death compared to those treated with VRd (hazard ratio: 0.59, 95% confidence interval: [0.42-0.82]). Conclusions: Findings from the MA indicate that DRd is associated with a lower risk of disease progression/death compared to VRd as 1L treatment for TIE patients with NDMM. These findings could help inform the selection of optimal 1L treatment for these patients in the absence of head-to-head clinical trials.

Patients with Sickle Cell Disease Can Demonstrate a Constellation of Symptoms Associated with Hyper-Hemolysis without Recent Transfusion

Background A hallmark characteristic in patients with Sickle Cell Disease (SCD) is chronic hemolysis, the severe exacerbation of which has been linked to RBC transfusion in some cases. This hyper-hemolysis (HH) is defined as a rapid decline of hemoglobin (Hb) and HbA% below pre-transfusion values. HH has been considered a severe form of antibody negative DHTR (Ab (-) DHTR) in patients with SCD and defined by the American Society of Hematology as hemolysis within 21 days of transfusion, negative DAT and absence of new alloantibody. Herein, we present a case series of 5 SCD patients with transfusion &amp;gt; 21 days from presentation demonstrating symptoms and lab findings consistent with HH. The purpose of this study is to characterize patients with SCD diagnosed with HH as a working diagnosis without temporal relation to transfusion. To our knowledge, this is the first and largest case series of its kind. Methods An IRB approved retrospective EMR review collected demographic and clinical data for patients with SCD admitted for concern for HH or DHTR to a large multi-site Pediatric Hospital in the Southeastern USA (2020-2023). All patients in this study were identified from Transfusion Medicine consults to investigate DHTR. Patient admission diagnosis was obtained from EMR review. Findings Cohort patients were 15-19 years with HbSS or HbS-beta thalassemia zero. All patients had transfusion &amp;gt;21 days from presentation. Of note, patient #5 received a transfusion during their first admission and was readmitted for signs and symptoms of HH/Ab (-) DHTR within 24hrs of discharge. All patients admitted for &amp;gt;1 day demonstrated an average 47% fall in hemoglobin (range: 24-69%), negative antibody screen/DAT, reticulocytopenia and mild to moderate thrombocytopenia. Four patients demonstrated elevated LDH. One patient died prior to discharge. Day of stay (DOS) of labs is in brackets []. Refer to table 1 for detailed patient data. Conclusion This case series demonstrates that patients with SCD can experience a constellation of symptoms identified in patients with HH without temporal relation to transfusion. These include hemolysis, reticulocytopenia, and thrombocytopenia as well as elevation of complement proteins. Given the overlap in presentation, HH in patients with SCD should be considered independently of proximity to transfusion for prompt diagnosis. Further study should include a retrospective review for further characterization. In addition, given the finding of elevations in C5a, further study into complement as a mechanism and target of therapy would be valuable.