Adult Sickle Cell Disease Patients Research Articles

Near-Infrared Spectroscopy Demonstrates the Benefit of Erythracytapheresis in Sickle Cell Disease Adult Patients with Cerebral Vasculopathy.

Cerebral vasculopathy can induce chronic cerebral hypoperfusion leading to stroke in patients with sickle cell disease (SCD) and is treated by blood exchange transfusion (BET). However, no prospective clinical study has demonstrated the benefit of BET in adults with SCD and cerebral vasculopathy. Near Infrared Spectroscopy (NIRS) is a recent non-invasive method complementary to Magnetic Resonance Imaging (MRI). We evaluated cerebral perfusion using NIRS during erythracytapheresis in patients with SCD with and without steno-occlusive arterial disease. We conducted a monocentric, prospective study in 16 adults with SCD undergoing erythracytapheresis in 2014. Among them, 10 had cerebral steno-occlusive arterial disease. NIRS measured the relative amounts of oxyhemoglobin (OxyHb), deoxyhemoglobin (DeoxyHb) and total hemoglobin (Total Hb) in brain tissue and in muscle. In cerebral hemispheres associated with steno-occlusive arterial disease, we observed a significant increase of OxyHb and Total Hb during BET, without modification of DeoxyHb. Using NIRS during BET showed that BET improves cerebral perfusion in adult patients with SCD with cerebral vasculopathy.

Physical, Mental, and Social Health of Adult Patients with Sickle Cell Disease after Allogeneic Hematopoietic Stem Cell Transplantation: A Mixed-Methods Study

Patients with sickle cell disease (SCD) experience a considerable physical and psychosocial disease burden. In recent years, the application of allogeneic hematopoietic stem cell transplantation (HSCT) to treat adults with SCD has increased. A thorough understanding of patients' physical, mental, and social health before and after cure is needed to meet the needs of this growing group of patients. We aimed to explore the perspectives of adult SCD patients on the changes in their experienced health and personal life goals after being cured. A mixed-methods approach was used, comprising a semistructured interview and a set of 9 Patient Reported Outcomes Measurement Information System (PROMIS) measures. Adult SCD patients who underwent HSCT at least 1 year earlier were eligible to participate in the study. Interviews were thematically analyzed using MAXQDA software. PROMIS T scores were compared with reference scores of the general population using SPSS Statistics. Ten patients participated in the study; their median age was 29.5 years (range, 19 to 49 years), and their median time since HSCT was 2.7 years (range, 1.0 to 3.5 years). Themes from the interviews were (1) pain/living pain free, (2) physical well-being, (3) mental well-being, (4) perspective/ outlook, (5) education/work, (6) family/friends, and (7) activities/participation. Following the PROMIS framework, we described these themes in a narrative synthesis according to health domain and categorized in 4 chronological time phases: before HSCT, first year post-transplantation, current situation, and future expectations. Physical health improved greatly, but transplantation-related toxicity, ongoing pain from avascular osteonecrosis, and fatigue negatively impacted quality of life in some patients. Furthermore, emotional struggles during the post-transplantation period were common, and patients expressed a need for psychological help. Patients reported improvements in social health and the ability to pursue personal life goals. The mean T scores of all PROMIS measures fell within the normal symptom limits compared with reference data of the general population, although, large variations were observed among the participants, matching our qualitative findings. In general, adult SCD patients experienced improved physical, mental, and social health after cure by HSCT and were able to pursue personal life goals. Yet they found themselves confronted with a new and unfamiliar reality that brought different challenges. Pain due to irreversible avascular osteonecrosis continued to have a negative impact. Clinicians should aim to help patients have realistic expectations before transplantation and offer timely psychological care.

Associations of hemolysis and anemia with cardiopulmonary dysfunction in an adult sickle cell disease cohort

BackgroundHemolysis contributes to the anemia of sickle cell disease (SCD). Hemolysis and anemia are distinct but inter-related pathophysiological processes that underlie end-organ dysfunction in this condition. We hypothesized that real-world medical tests would reveal distinct contributions of hemolysis and anemia to certain cardiopulmonary changes in adults with SCD. MethodsWe assessed laboratory and clinical tests of cardiopulmonary function obtained during routine delivery of care in 442 adult SCD patients. We characterized hemolysis by the first principal component (PC1) of reticulocyte percent, lactate dehydrogenase (LDH), aspartate amino transferase (AST) and total bilirubin- the hemolytic component. The relationships of hemoglobin concentration and hemolysis to organ dysfunction were analyzed by multiple regression and path analysis to identify independent associations. ResultsDegree of hemolysis and degree of anemia both associated independently with elevated values for left atrial diameter (LAD) and left ventricular end-diastolic diameter (LVED), and with lower percent predicted forced expiratory volume in first second (FEV1). Degree of hemolysis, but not anemia, associated independently with low values for oxygen saturation, forced vital capacity (FVC), and total lung capacity (TLC)]. Path analysis reinforced the trend by multiple regression for association of both degree of hemolysis and anemia with elevated TRV but not with lower diastolic blood pressure. DiscussionAnalysis of real-world clinical tests suggest that, although they are inter-related, the degrees of hemolysis and of anemia make independent contributions to cardiopulmonary dysfunction and that treatments that specifically target both aspects of sickle cell disease may be of maximal benefit.

Comparative study between chronic automated red blood cell exchange and manual exchange transfusion in patients with sickle cell disease: A single center experience from Saudi Arabia.

Red cell transfusion remains the gold standard in managing sickle cell disease (SCD) with severe complications. Offering red blood cell exchange (RBCX) either manual exchange transfusion (MET) or automated RBCX (aRBCX) can reduce the complications of chronic transfusion and maintain target Hb thresholds. This study audits the hospital experience of overseeing adult SCD patients treated with RBCX, both automated and manual, and compares the safety and efficacy. This retrospective observational study was conducted as an audit for chronic RBCX for adult patients with SCD in 2015-2019 at King Saud University Medical City, Riyadh, Saudi Arabia. A total of 344 RBCX for 20 adult SCD patients who were enrolled in regular RBCX, (11/20) patients had regular aRBCX with a total of (157) sessions, and (9/20) patients had MET with a total of (187) sessions. The median level of HbS% post-aRBCX was significantly lower than MET (24.5.9% vs. 47.3%, P < 0.010). Patients on aRBCX had fewer sessions (5 vs. 7.5, P < 0.067) with better disease control. Although the median yearly pRBC units per patient for aRBCX was more than the double needed for MET (28.64 vs. 13.39, P < 0.010), the median ferritin level was 42 μg/L in aRBCX versus 983.7 μg/L in MET, P < 0.012. Compared to MET, aRBCX was more effective in reducing HbS, with fewer hospital visits and better disease control. Although more pRBCs were transfused, the ferritin level was better controlled in the aRBCX group without increasing alloimmunization risk.

A clinico-hematological study of sickle cell disease among adult patients in Makkah, Saudi Arabia.

Background: Sickle cell disease is an autosomal recessive disease characterized by an aberrant production of hemoglobin S (HbS). The disease's presentation and severity varied substantially between people from various socioeconomic backgrounds and geographical regions. The clinical picture includes hemolytic anemia, vascular occlusion events, acute and persistent pain, and varied organ damage. Objective: To investigate the clinical and hematological characteristics of adult sickle cell disease patients. Methodology: The study was conducted utilizing outpatient and inpatient data obtained retrospectively from a specialist hospital in Makkah city from January 2019 to December 2019. This study collected clinical and hematological data from all patients of sickle cell anemia (SCA) validated by high performance liquid chromatography (HPLC) between the ages of 18 and 50. The data was gathered from the laboratory database and contains demographic and hematological findings of CBCs performed on a fully automated hematology analyzer, as well as HPLC results for percentages of variant hemoglobins within the sickle cell anemia group. This study comprised a total of 130 participants with sickle cell anemia. All of the above patients' clinical findings were documented from the hospital archives. Results: The mean age for all the patients was 30.5±11.1 years. Pearson correlation for male patients showed significant positive correlations between hemoglobin-S and leucocytes (r= 0.503, P

Should Magnetic Resonance Angiography Be Used for Screening of Intracranial Aneurysm in Adults with Sickle Cell Disease?

Magnetic resonance imaging (MRI) is used in patients with sickle cell disease (SCD) to detect silent cerebral infarcts. MR angiography (MRA) can identify arterial stenoses and intracranial aneurysms (ICANs) associated with SCD. In this study, we aimed to estimate the prevalence of ICANs in asymptomatic adult patients with SCD referred from the SCD clinic for routine screening by MRI/MRA using a 3T-MRI scanner. Findings were independently reviewed by two neuroradiologists. Between 2016 and 2020, 245 asymptomatic adults with SCD were stratified according to genotype (SS/S-β0thalassemia and SC/Sβ+). ICANs were found in 27 patients (11%; 0.95 CI: 8-16%). ICANs were more frequent in SS/S-β0thalassemia patients (20/118 or 17%; 0.95 CI: 11-25%) than in SC/βb+ patients (7/127 or 6%; 0.95 CI: 2-11%; p = 0.007). Individuals with SCD (particularly SS/S-β0thalassemia) have a higher prevalence of ICANs than the general population. We believe that MRA should be considered in the current American Society of Hematology guidelines, which already contain a recommendation for MRI at least once in adult SCD patients. However, the clinical significance of preventive treatment of unruptured aneurysms remains controversial.

Clinical and laboratory characterization of adult sickle cell anemia patients in Kinshasa.

Sickle cell anemia (SCA) is a monogenic hemoglobinopathy associated with severe acute and chronic complications, with the highest incidence worldwide in Sub-Saharan Africa. The wide variability in clinical manifestations suggest that a uniform response to hydroxurea may not be attained. In view of a potential treatment with hydroxyurea (HU), we assessed the variability of clinical and hematological manifestations in a cohort of adults with SCA in Kinshasa, capital of the DR Congo in Central Africa. A cross-sectional study was conducted in a hospital dedicated to SCA management in Kinshasa. Clinical history of patients was recorded, a complete physical examination performed. The diagnosis was confirmed by means of DNA analysis. A full blood count and hemolysis markers were measured. The severity of the disease was evaluated by means of a previously reported score. The study group consisted of 166 genetically confirmed SCA patients. The SCA severity was mild in 28.9%, moderate in 64.5% and severe in 6.6%. The disease severity score increased with patient's age (p ≤ 0.001). The severity was higher in males compared to females (p = 0.012). In males, the severity score was correlated with the presence of priapism (p = 0.045), a manifestation not previously incorporated in the severity score. The severity score was inversely correlated with the fetal hemoglobin (HbF) rate (p = 0.005). Malnutrition (BMI <18.5 kg/m2) was present in 47% of patients and was related to the male sex, hip disease (aOR 3.11; p = 0.019) and severe phenotype (aOR 3.53; p = 0.012). Leg ulcers were more frequent in males than in females (p = 0.001; OR 24.3) and were correlated with the number of days of hospitalization (p = 0.029). Hip disease was related to the increasing age (p = 0.008). In this selected, hospital-based populations of adults with SCA, severe disease was rare, which may be due to survival bias. However, two thirds had moderate severity of the disease, mostly with a low HbF, and they may benefit from HU treatment. In the Central-African setting the separation between vaso-occlusive and hyperhemolytic sub-phenotypes was not applicable.

IF IM in a crisis: Intranasal fentanyl versus intravenous morphine in adult vaso-occlusive crisis

ImportanceStudies have demonstrated the benefits of INF in reducing pain scores in pediatric patients with VOC due to sickle cell disease (SCD) and in adult patients with chronic pain conditions other than VOC, such as cancer. However, there is limited literature that exists describing the role of INF in adult patients with VOC due to SCD. Current literature demonstrates that the use of IV morphine for VOC patients leads to reduced pain. Therefore, comparing the use of INF with IV morphine will establish the degree of effectiveness of INF for VOC patients. ObjectiveTo determine if intranasal fentanyl is equally as effective as IV morphine for treating VOC-associated pain in adult SCD patients. DesignThis study was a retrospective non-inferiority cohort study. Electronic health records were utilized to identify eligible patients between January 1, 2021 to February 28, 2022. Patients who received INF as an initial opioid upon presentation to the ED where allocated to the intervention group. On the other hand, individuals who received IV morphine as an initial opioid upon presentation to the ED were allocated to the control group. SettingA multi-site healthcare system containing five hospitals. ParticipantsPatients 18 years of age or older, admitted to the ED with VOC due to SCD, and received INF or IV morphine as an initial opioid upon presentation to the ED. Main outcomes and measuresThe primary outcome was to evaluate the percent change in pain reduction after the initial dose of opiate between groups. Secondary outcomes include time to first rescue medication, total morphine milligram equivalent (MME) of IV opiates, hypotension, bradycardia, respiratory distress requiring opiate reversal within 6 h post- study drug administration, readmission within 48 h, and ED disposition. ResultsA total of 230 patients were reviewed within the study period, 95 subjects met inclusion criteria, 31 subjects were included in the INF arm and 64 subjects in the IV morphine arm. The primary outcome showed an average percent pain reduction of 17.25% in the INF arm and 17.15% in the IV morphine arm. The point estimate difference was 0.1% (95% CI −9.3%–9.5%; non-inferiority (p < 0.0001). The median dose of IV opiates was 8 MME in the INF group, and 6 MME in the IV morphine group (p = 0.0268). The time from study drug to first rescue medication administration was 22.4 min and 27.3 min in the INF and IV morphine groups, respectively (p = 0.2231). There was no incidence of hypotension or respiratory distress requiring opiate reversal in either arm. Bradycardia occurred in 12.9% and 7.7% (p = 0.2042), readmission rates within 48 h due to VOC was 6.5% and 20.9% (p = 0.0553), and discharge from the ED to home was 16% and 66% (p = 0.0196) in INF and IV morphine arms, respectively. ConclusionINF provided similar pain reduction compared to IV morphine in the treatment of adults with VOC presenting to the ED. IV morphine arm showed a statistically significant difference in discharge to home from the ED, however there was a trend in readmission within 48 h. The study showed no significant difference in hypotension, respiratory distress, or bradycardia between the groups. The INF group had no significant impact on time to drug administration compared to IV morphine, however it was within 1 h of patient presentation which complies with American Society of Hematology (ASH) guidelines. In conclusion, our study showed that INF was non-inferior when compared to IV morphine in reducing pain scores after drug administration. Therefore, INF is an effective alternative to IV morphine for pain management in adults presenting to the ED for VOC particularly in those with limited IV access.

Accessible Care with High Patient Satisfaction: Telemedicine Use in Sickle Cell Disease.

Background: The COVID-19 pandemic necessitated a rapid transition to telemedicine, providing a critical opportunity to study telemedicine satisfaction and usability in patients with sickle cell disease (SCD). Methods: A cross-sectional survey was completed by 99 adult SCD patients who participated in at least one telemedicine visit between March and July 2020. Telemedicine satisfaction and usability were assessed with the Telemedicine Satisfaction Questionnaire (TSQ) and System Usability Scale (SUS), respectively. Preference for video visits was assessed with a 1-10 rating scale, with 10 indicating the highest preference. Measures of anxiety, depression, and patient activation were also assessed. Linear and logistic regressions were performed to evaluate for socioeconomic and psychosocial correlates of telemedicine satisfaction, usability, and preference. Results: Participants were 72% women, with a mean age of 39 years. The median (interquartile range [IQR]) TSQ was 56 (52-64) out of 70, indicating high satisfaction. The median (IQR) SUS was 72.5 (62.5-82.5) out of 100, indicating above average usability. Participants tended to prefer video visits for regular care (median [IQR] rating of 7 [5-9]) but not for management of acute pain (median [IQR] rating of 4 [2-8]). Neither satisfaction nor usability was associated with age or mental health. Telemedicine usability was positively associated with having private insurance compared with public insurance. Higher scores on both satisfaction and usability were associated with higher patient activation. Conclusions: Adults with SCD report good usability and high satisfaction with telemedicine, across multiple demographic groups. Therefore, telemedicine has valuable potential to improve access to high-quality care for these patients.

Improved T-Cell Chimerism and Successful Withdrawal of Immunosuppression after Non-Myeloablative Stem Cell Transplantation for Sickle Cell Disease with Azathioprine/Hydroxyurea Preconditioning Added to Alemtuzumab/TBI Conditioning

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only established curative treatment option for sickle cell disease (SCD). In adult SCD patients, myeloablative conditioning is associated with significant toxicity, primarily because of cumulative organ damage. Recently, matched sibling donor (MSD) transplantation with non-myeloablative conditioning (alemtuzumab/3 Gy total body irradiation (TBI)) showed promising outcomes in adult SCD patients. This chemotherapy-free regimen, typically resulting in mixed chimerism, is associated with mild toxicity with no reports of graft-versus-host disease (GvHD). Despite mixed chimerism, the red blood cell (RBC) phenotype is completely donor-derived. However, in a large series, 13% of patients experienced graft failure. Another 8.2% of patients could not stop their immunosuppression (sirolimus) after one year, because of low donor T-cell chimerism (<50%). Reported mean donor T-cell chimerism at 12-months post-transplantation was 48% (Br J Haematol. 2021 Feb;192(4): 761-768). We hypothesized, that the addition of azathioprine and hydroxyurea as preconditioning to the alemtuzumab/TBI conditioning regimen will reduce the risk of graft failure and improve donor T-cell chimerism, enabling successful withdrawal of sirolimus in all patients. Aim: To investigate the effects of adding azathioprine/hydroxyurea preconditioning to alemtuzumab/TBI conditioning on donor chimerism levels and the occurrence of graft failure in adult SCD patients receiving non-myeloablative MSD-HSCT. Methods: Adult SCD patients with an available HLA-identical sibling donor were eligible for this treatment. All patients received three months of azathioprine 150mg qd and hydroxyurea 25mg/kg qd preconditioning. After exchange transfusion (target HbS <30%), conditioning with alemtuzumab 1mg/kg total dose and 3Gy TBI started on day -7, followed by unmanipulated peripheral hematopoietic stem cell infusion on day 0. Sirolimus as GvHD and rejection prophylaxis started on day -1. Results: Twenty SCD patients (median age 26 (range 19-49) years) were transplanted with a median follow-up of 24.5 months (range 1-52 months). Patient and transplant characteristics are shown in Table 1. Median donor myeloid and T-cell chimerism of engrafted patients was 100% (range 87-100%) and 68.5% (range 37-89%) at 12-months post-transplantation and 94% (range 86-100%) and 78.5% (range 68-88%) at 18-months post-transplantation, respectively (Figure 1). These donor T-cell chimerism percentages are higher than previously reported with alemtuzumab/TBI conditioning only. All engrafted patients had a corrected SCD phenotype with normalized hemoglobin levels. Importantly, all patients with a follow-up of ≥ 12 months (n=12) could successfully taper and stop sirolimus without decreases in donor chimerism. One year estimated disease-free survival and overall survival were 94.7%. and 93.3%, respectively. One patient (5%) experienced graft failure without autologous regeneration and subsequently died after a series of complications, including EBV reactivation, post-transplantation lymphoproliferative disease, and systemic aspergillosis. Acute gastrointestinal GvHD grade 2 occurred in one patient (5%) and resolved quickly after treatment with prednisolone. Summary/Conclusion: Azathioprine/hydroxyurea preconditioning prior to alemtuzumab/TBI resulted in improved donor T-cell chimerism, potentially reducing the risk of graft failure after non-myeloablatieve MSD transplantation in SCD patients. Importantly, all engrafted patients reached donor T-cell chimerism >50% and were able to stop immunosuppressives as scheduled. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Effect of ABO Mismatch and RBC Alloimmunization on the Outcomes of Patients with Sickle Cell Disease Undergoing Hematopoietic Stem Cell Transplantation

Background: Hematopoietic stem cell transplantation (HSCT) remains the only well-established curative option for sickle cell disease (SCD) patients. Non-myeloablative (NMA) conditioning has been used to improve the outcomes and reduce toxicities in adult SCD patients. However, Recipient/Donor (R/D) ABO incompatibility and alloimmunization could be significant impediments to successful outcomes when transplanting SCD patients due to risks of hemolysis, delayed engraftment, poor graft function and graft failure (GF). Herein, we report our experience with allogeneic HSCT for SCD and the effects of RBC groups mismatch and alloimmunization on the outcome of transplanted patients. Methods: We conducted a retrospective analysis of all adolescents and adult SCD patients (age >14 year) that underwent HSCT from January 2015 to February 2022 at our center. All patients received Intravenous alemtuzumab (1 mg/kg divided over 5 days on days -7 to -3) and 300 cGy TBI on day -2 or -1 for conditioning. Pre-transplant preparation consisted of hydroxyurea at maximum tolerated dose for 2-3 months and one session of exchange transfusion. Peripherally mobilized stem cells targeting 10x106 /kg of CD34 cells were used. For graft versus host disease (GVHD) prophylaxis sirolimus was started on day -1 and continued for one year with tapering if lymphoid chimerism was > 50%. For Patients with major ABO incompatibility, we administered 2 doses of rituximab (375 mg/m2) and 3 sessions of plasmapheresis before starting the conditioning regimen targeting an isoheamagglutinin titer < 1/32. The primary objective was to determine the impact of RBC groups mismatch and alloimmunization on the outcome of transplanted patients. The secondary objective was to assess the impact of GF on overall survival (OS). Logistic regression was done to evaluate predictors for GF. Kaplan-Meier method was used for survival analysis. Results: A total of 194 patients were included with a median age of 26 years and 55.6% being males. The median baseline Hgb and HbS were 93 g/L and 71.3%, respectively. Indications of stem cell transplantations were most commonly due to recurrent vaso-occlusive crisis in 52.57% of patients, CNS disease in 19.58%, and acute chest syndrome in 17.01%. Other indications included sickle nephropathy, sickle hepatopathy, priapism and AVN in 10.82% of patients collectively. Around 59% of donors were sickle cell disease carriers, and 41% were healthy donors. After a median follow up of 28.8 months (5-83), sixteen patients (8%) experienced graft failure (3 with primary GF and 13 with secondary GF). On univariate analysis (table 1a), ABO minor incompatibility (odds ratio (OR), 3.63; 95% confidence interval (CI), 1.13 -11.65, P=0.029, and RBC alloantibodies against donor non-ABO antigens (OR, 4.22; 95% CI, 1.17 -15.14, P=0.039) were predictive for GF. However, on multivariate analysis (table 2a), only RBC alloantibodies against donor non-ABO antigens (OR, 8.29; 95% CI, 2.01 to 34.05, P=0.0033) was predictive of GF. None of the 16 patients with major ABO incompatibility developed GF. Two-years OS for all patients was 95%. The median OS for patients with GF was 98% compared to 74% patients without GF, P<0.0001) (Figure 1). Conclusion: In our SCD transplanted patients, RBC alloantibodies against donor non-ABO antigens was an independent risk factor for GF. Patients with GF had an inferior survival and strategies for decreasing the risks are needed. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Quality of Life and Personal Life Goals of Adult Sickle Cell Disease Patients after Curative Allogeneic Stem Cell Transplantation: A Mixed Methods Study

Introduction: Sickle cell disease (SCD) is associated with poor quality of life (QoL) and early mortality. In the Netherlands, allogeneic hematopoietic stem cell transplantation (HSCT) as curative treatment option for adult SCD patients was first introduced in 2018. A thorough understanding of the impact of undergoing HSCT on QoL is essential for health care professionals to be able to meet the needs of this patient population. Aim: To explore the perspectives of adult SCD patients on the impact of curative HSCT on physical, mental, and social health. Methods: Adult SCD patients who underwent HSCT at the Amsterdam UMC ≥ 1 year ago were eligible for this study. A mixed methods approach consisting of an exploratory qualitative design and a questionnaire component was used. All patients participated in a semi-structured interview on their experienced QoL and personal life goals. Interviews were audio recorded, transcribed, and coded using MAXQDA® software. Results were analyzed using Thematic Analysis. Additionally, participants completed a Patient Reported Outcome Measurement Information System (PROMIS®) questionnaire measuring 9 item banks on physical, mental, and social health at the time of the interview. Results of the PROMIS® questionnaires (T-scores) were related to reference T-scores of the general Dutch population using descriptive statistics (IBM SPSS statistics 28.0). Results: Ten SCD patients with a median age of 29.5 years (range 19-49) participated in the study between October 2021 and May 2022. The median time since HSCT was 2.7 years ranging from 1 to 3.5 years. Mean T-scores of all participants fell within normal limits for all 9 PROMIS® item banks, as compared to the Dutch general population (Table 1). However, T-scores varied between patients. Two patients with serious avascular bone necrosis (AVN), developed prior to HSCT, scored mild, moderate, or severe on ≥7 of 9 item banks. Another patient scored mild or moderate on all 3 mental health item banks. These differences between patients, as well as a general satisfaction with their current QoL despite having experienced physical and psychosocial difficulties were reflected in the outcome of the interviews. Eight central themes emerged from the Thematic Analysis: (1) pain, (2) physical wellbeing, (3) mental wellbeing, (4) perspective, (5) counseling/guidance, (6) education and work, (7) family and friends, and (8) activities and participation. These themes were categorized in mental, physical, and social health, following the PROMIS framework, and subsequently described based on four phases: before HSCT, HSCT - 1st year post transplantation, current situation, and future expectations. Most patients reported to experience improved physical, mental, and social health after HSCT and being able to set and achieve personal life goals. However, many participants also described an (ongoing) mental impact of having had SCD their whole life even after curation by HSCT. They expressed a clear need for psychological counseling before, during, and after HSCT. Furthermore, persistence of pain due to AVN had a negative influence on the perceived physical health of some patients. Several patients experienced a discrepancy between their expectations of HSCT and the outcome; either above- or below-expected. Conclusion: QoL of adult SCD patients who underwent curative HSCT seemed generally comparable to the Dutch general population; patients reported to experience improved QoL, and the ability to pursue personal life goals. However, the physical, mental, and social impact after curation can be extensive, ranging from positive to negative and differed between patients. Patients expressed a need for psychological support before, during, and after HSCT. Moreover, irreversible SCD-related organ damage can negatively influence the QoL of transplant recipients and patient expectations should be actively discussed by health care professionals before HSCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Inpatient Reliance Ratio Versus Emergency Department Reliance Ratio in a Sickle Cell Disease Medical Home

Background: The Emergency Department (ED) Reliance Ratio (ERR, defined as ED visits/ED + ambulatory + inpatient visits) measures the percentage of all health care visits that occur in the ED in relation to primary care, including avoidable ED visits, and may therefore discriminate among high-ED-user populations. Adults with sickle cell disease (SCD) are known to have high ERR (by convention, >0.33), likely driven by a complex mix of factors. Like in other ambulatory-care-sensitive conditions, intense SCD ambulatory case management may drive down the ERR. But we found no validated measure of hospital utilization percentage analogous to the ERR. We therefore created the inpatient reliance ratio (IRR, defined as inpatient visits/ED + ambulatory + inpatient visits), as the percentage of all health care visits that occur in the hospital in relation to primary care and ED care, including avoidable hospital visits. We tested the performance of the ERR versus the IRR in an adult SCD sample. Method: In 2018, as part of a multi-component intervention in an SCD Adult Medical Home, we assigned Patient Navigators (PNs), as case managers to each of the program's top 50 highest utilizers, but also began periodically managing the remaining medical home patients ad hoc. Services provided included behavioral health services, dedicated inpatient care, an infusion unit, and inpatient and ED individualized care plans. The study sample was Adult SCD patients at Virginia Commonwealth University from 2011-2021 (annual N's from 299 to 641). Using Analysis of Variance, we studied the effect of the intervention over time on total annual charges, the annual ERR, and the annual IRR. We also performed Spearman's correlations associating annual total charges with either annual ERR or annual IRR. Last, we performed linear regression with annual total charges as the outcome variable (linearly distributed), to test the relative predictive contribution of ERR vs. IRR. Results: (Figure 1) After increasing steadily from 2011-2017 pre-program onset, both the annual ERR and the annual IRR decreased roughly successively from 2017-21 (ANOVA p-value=0.0089 for ERR, ANOVA p-value=0.0002 for IRR). Annual total charges correlated strongly with ERR (Spearman R=0.44, P<0.0001) but more strongly with annual IRR (Spearman R=0.64, P-value<0.0001). Similarly, linear regression indicated that IRR contributed more strongly to annual total charges than did ERR (beta coefficients = 97906 vs 23175). Conclusion: We demonstrate that the IRR, similar to the ERR, appears to be a measure of avoidable care: It varies as a function of total costs, but it is sensitive to intense ambulatory case management. It more closely correlates with total costs and more closely predicts total costs than the ERR. The benchmark for what makes a high or low IRR has not been defined as it has for ERR. But future studies could further show its relationship to utilization management and get population norms to set an appropriate management goal for the IRR. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Real-World Outcomes in Adult Sickle Cell Disease Patients Treated with Crizanlizumab, Voxelotor or Both

Background Crizanlizumab and voxelotor are new disease modifying therapies that have been shown respectively as single agents to reduce the frequency of vaso-occlusive crises (VOCs) and improve anemia. Clinical effects of these drugs in combination have not been examined in clinical trials. Objectives Evaluate the rates of VOC-related acute care utilization, lengths of stay (LOS) of hospitalizations and hemoglobin levels in sickle cell disease (SCD) patients treated with crizanlizumab, voxelotor, or both. Methods A single center, retrospective chart review was performed of all adult SCD patients to identify those treated with crizanlizumab and voxelotor, alone and in combination, for at least 12 months. Number of acute care utilization visits which includes emergency department (ED) visits, infusion room visits and hospitalizations for management of VOCs, lengths of stay of hospitalizations, as well as steady state hemoglobin values in the 12 months before and after initiation of crizanlizumab, voxelotor, or both were obtained for each patient. Acute care visits and hospitalizations for management of conditions other than acute VOC were excluded. A descriptive analysis was conducted to summarize patient characteristics and outcomes including changes from baseline over time for the three treatment groups separately. Fisher's exact tests were applied to compare categorical variables among the three treatment groups. Kruskal-Wallis tests were used instead for outcomes at a given time point or changes from baseline. A significant Kruskal-Wallis test was followed by pairwise Dunn tests adjusted for multiple testing using the Benjamini-Hochberg method. P-values smaller than 5% were considered statistically significant. All the statistical analyses were performed in R version 4.1.2. Results Of 266 adult SCD patients, 77 (29%) had ever taken crizanlizumab, voxelotor or both. 48 out of 77 (62%) patients met inclusion criteria of being on these therapies alone or in combination for at least 12 months. Of the included patients, 19 patients were treated with crizanlizumab alone, 18 patients were treated with voxelotor alone, and 11 patients were treated with both crizanlizumab and voxelotor. Baseline characteristics are summarized by treatment group in Table 1. Patients on crizanlizumab alone had a broader distribution of hemoglobin genotypes with a significantly smaller proportion having the Hb SS genotype (42.1%) compared to those on voxelotor alone (88.9%) or on a combination of crianlizumab and voxelotor (81.8%). Age, gender, and hydroxyurea (HU) use were not statistically significantly different among the three treatment groups. There was no statistically significant difference in acute care utilization in patients on crizanlizumab, voxelotor, or both (Table 2). Specifically, there was no evidence of difference in VOC related ED visits, infusion room visits, hospitalizations and LOS in the 12 months following initiation of these therapies compared to the 12 months preceding it. Of note, in patients on both crizanlizumab and voxelotor, the mean number of VOC related hospitalizations before initiation of treatment was 2.45 ± 2.54 compared to 1.18 ± 1.78 after, although these results did not reach statistical significance (P = 0.189). Likewise, the Mean total LOS before initiation of treatment was 12.18 ± 12.80 days compared to 6.45 ± 10.99 days after, although the results also did not reach statistical significance (P 0.274). At the 12 month mark, there was a significant difference in the distribution of change in hemoglobin level among the three treatment groups (P=0.008) (Table 2). Specifically, when compared to baseline hemoglobin, patients on voxelotor alone had a greater increase in hemoglobin than those on crizanlizumab alone (0.90 ± 1.19 g/dl vs -0.17 ± 0.56 g/dl, P = 0.008). Similarly, when compared to baseline hemoglobin, patients on both crizanlizumab and voxelotor had a greater increase in hemoglobin than those on crizanlizumab alone (0.70 ± 1.03 g/dl vs -0.17 ± 0.56 g/dl, P = 0.010). Conclusion This study suggests that patients treated with both crizanlizumab and voxelotor had an improvement in number of VOC related hospitalizations, LOS and hemoglobin level but our results could not achieve statistical significance due to our small sample size. Further real-world studies are needed to further understand the effects of combination therapies on acute care utilization. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

An Endogenous Metabolic Modulator Composition Improves Hydration Status and Decreases Adhesion Properties of Red Blood Cells from Patients with Sickle Cell Disease

Background Sickle cell disease (SCD) is a group of hemoglobinopathies caused by point mutations in the β-globin gene leading to abnormal red blood cells (RBCs). There are various forms of SCD; sickle cell anemia (SCA) is characterized by homozygosity for hemoglobin (Hb) S (HbSS) whereas HbSC disease results from compound heterozygosity for HbS and HbC. HbC does not lead to RBC sickling, but induces loss of intracellular K+ and H2O causing RBC dehydration. Similarly, in HbSS RBCs, through dehydration, an increase of the intracellular concentration of poorly soluble HbS enhances polymerization upon deoxygenation, causing RBCs to become rigid and to sickle. Until recently, the only approved therapy for SCD was hydroxyurea (HU). HU increases fetal Hb (HbF) levels and improves RBC hydration and deformability. For decades, amino acids have been explored as potential treatment to restore the disrupted pathophysiological pathways in SCD. RCitNacQCarLKHVS, an Endogenous Metabolic Modulator (EMM) composition of ten different amino acids and derivatives, was designed to target and support RBC metabolism. In this study, we investigated the effect of ex vivo treatment of this EMM on RBC properties and function in SCA and HbSC. Methods Blood of 12 different adult SCD patients (9 HbSS [of whom 6 were on chronic RBC exchange (RBCX)], 3 HbSC) and 2 healthy controls was collected. Whole blood was incubated at standardized hematocrit (20%, patient plasma) in the presence or absence of different RCitNacQCarLKHVS concentrations for 4h at 37°C. Routine hematological parameters were measured using the Cell-Dyn Sapphire (Abbott Diagnostics). Percentage of total dense RBCs (%DRBCs) was analyzed from 10/12 patients (4 HbSS on RBCX, 3 HbSS not on RBCX, 3 HbSC) using the Advia 120/2120 hematology analyzer (Siemens Healthcare Diagnostics). Point of sickling (PoS), RBC deformability (EImax), and hydration status (Ohyper) were assessed by oxygen gradient ektacytometry and osmotic gradient ektacytometry, respectively, in 12/12 patients using the Lorrca (RR Mechatronics). Blood viscosity was measured in 6/12 patients (3 HbSS not on RBCX and 3 HbSC) at 37°C using a cone-plate viscometer (Brookfield). The hematocrit-to-viscosity ratio (HVR) was calculated as follows: hematocrit/blood viscosity at 300 s-1. RBC adhesion to laminin (BioLamina) was assessed in 4/12 patients (3 HbSS not on RBCX, 1 HbSC) using a microfluidic device (IBIDI μ-Slide VI 0.4). Statistical analysis was performed in Graphpad Prism v9.3.0 using the Friedman test. Results Ex vivo treatment of blood of SCD patients with RCitNacQCarLKHVS showed a significant dose-dependent increase in Ohyper as measured by osmotic gradient ektacytometry (Figure 1), indicating an improvement of RBC hydration status of SCD RBCs. This was accompanied by a significant increase in mean corpuscular volume (MCV) and reduction in mean corpuscular Hb concentration (MCHC). RBCs of healthy controls showed a similar trend in Ohyper, MCV and MCHC. In addition, %DRBCs showed a significant dose-dependent decrease in both HbSS and HbSC RBCs as a result of RCitNacQCarLKHVS treatment. Oxygen gradient ektacytometry showed a significant increase in maximum deformability (EImax), but no significant change in point of sickling. The HVR did not significantly change during dose-response experiments. Median RBC adhesion to laminin decreased as a result of ex vivo treatment with RCitNacQCarLKHVS (Figure 2). Conclusion Ex vivo treatment with RCitNacQCarLKHVS demonstrated a significant dose-dependent increase in RBC hydration (Ohyper, MCV, MCHC and %DRBCs), deformability (EImax) and decreased adhesion properties in SCD RBCs. Dehydrated and dense RBCs with reduced deformability and increased adhesion are more prone to hemolysis, and associated with vaso-occlusive complications such as priapism, skin ulcers, and nephropathy. Results from this study therefore suggest benefit of EMM in modulating clinically-relevant rheological properties such as hydration state and adhesion of SCD RBCs in both SCA and HbSC. The fact that HVR did not change may represent an additional therapeutic benefit, especially for HbSC patients who have, in general, higher blood viscosity compared to HbSS patients. Moreover, it would be worthwhile to investigate if the concomitant use of select amino acid combinations with HU or other anti-sickling agents has an additional beneficial effect in SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Effect of Voxelotor on Cerebral Perfusion and Cerebral Oxygen Metabolism in Adult Patients with Sickle Cell Disease; Preliminary Results of the Coverage Study

Background: Sickle cell disease (SCD) is characterized by hemolytic anemia and a hyperdynamic circulation resulting in impaired cerebral hemodynamics and perfusion, culminating in ischemic damage of the brain. SCD is strongly associated with overt strokes or silent cerebral infarctions (SCI) which have been related to elevated flow in the median cerebral artery in children measured by transcranial Doppler. Patients with SCD have an increased cerebral blood flow (CBF) to maintain adequate oxygen delivery (OD). Previously, we and others have demonstrated with special MRI techniques that despite the maintained OD, cerebral metabolic rate of oxygen (CMRO2) is reduced in SCD due to reduced oxygen extraction fraction (OEF), which in turn is strongly related to CBF and hemoglobin (Hb) level. Voxelotor is a small molecule that reversibly binds to Hb and increases its oxygen affinity, thereby decreasing Hb polymerization and sickling. The resulting decreased hemolytic anemia can potentially ameliorate cerebral hemodynamics and perfusion, the increased oxygen affinity may reduce the offloading of oxygen. The aim of our study is to assess the effects of voxelotor on markers of cerebral perfusion and oxygen metabolism. In addition, the effect of voxelotor on the hyperdynamic cardiac function was assessed. Methods: This single-arm, interventional trial is being conducted in a tertiary hospital in Amsterdam, The Netherlands. Adult SCD patients with the severe genotypes of HbSS and HbSβ0-thalassemia were eligible for inclusion. Other major inclusion criteria were: Hb ≤ 10.5 g/dL and in case of hydroxyurea use, a stable dose for at least 90 days. Major exclusion criteria were: regular transfusions or a transfusion within 90 days prior to inclusion, hospitalization for vaso-occlusive crisis ≤ 14 days before inclusion. At baseline and after 3 months of voxelotor treatment (1500 mg pd), MRI scans, echocardiography and laboratory assessments were performed. Time-encoded arterial spin labeling was performed to obtain CBF measurements, gray matter CBF was derived by using white matter and gray matter masks. T2 relaxation under spin tagging was performed in order to calculate OEF. Oxygen delivery and CMRO2 were calculated: formula, CBF x OD, with the OD calculated from OEF and oxygen content. Maximal tricuspid regurgitation velocity (TRVmax) was assessed by trans-thoracic echocardiography as a marker of hyperdynamic circulation. N-Terminal pro-B-type natriuretic peptide (NT-proBNP) was measured as a marker of cardiac stress/dilatation. Parametric data are presented with mean and SD and analyzed by a paired T-test and non-parametric data with median and IQR, and analyzed by a Wilcoxon signed-rank test. Results: Preliminary results of 15 patients (HbSS/HbSβ0-thalassemia, 11/4, mean age 38 years (SD 10), 4 female) who completed their 3 month follow-up are presented here. Upon 3 months of voxelotor treatment, Hb levels significantly increased, 7.6 g/dL, (IQR 6.9 - 8.2) compared to 10.0 g/dL (IQR; p < 0.001), and hemolysis significantly reduced, represented by reticulocyte count, bilirubin and LDH levels (p = < 0.05; Table 1). After 3 months of treatment also a significant increase in oxygen delivery from 6.4 to 8.2 ml O2/100g/min (p = 0.006) was observed, which was primarily due to the increased Hb levels. However, CBF and CMRO2 did not change significantly after 3 months of voxelotor treatment (Table 2) while OEF decreased significantly at 3 months as compared to baseline (from 28.9% to 23.2%, p = 0.002) (Table 2). No significant changes in NT-proBNP levels and TRVmax were observed (Table 1) although a significant decrease was observed in patients with NT-proBNP-levels >160 at baseline (213 (IQR 161 - 254) ng/L vs 152 (IQR 50 -163) ng/L; p = 0.028)). Conclusion: In this preliminary study, no changes in cerebral hemodynamics (CBF) and oxygen metabolic rate (CMRO2) were observed, despite an increased cerebral oxygen delivery due to improvement of Hb levels. CMRO2 remained unchanged as a result of diminished OEF, based on the calibration according to the Li-Bush model, most likely due to the increased oxygen affinity attributed to voxelotor. With respect to the cardiac measures of the circulatory state, no effect on NT-proBNP levels and TRVmax was observed although a significant decrease in NT-proBNP-levels was observed in a post-hoc analysis of patients with elevated NTproBNP levels at baseline. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Individual Red Blood Cell Fetal Hemoglobin Concentrations Determined By Imaging Flow Cytometry and the Number of F Cells Are Very Good Predictors of Clinical Response to Increased Level of HbF and Are Associated with Hemolysis, Tricuspid Regurgitant Jet Velocity, and Sickle Retinopathy in Adult Sickle Cell Disease Patients

Sickle cell disease (SCD) patients with similar total fetal hemoglobin (HbF) levels may present with different severity, which is attributed to the heterogeneous distribution of HbF among red blood cells (RBCs) with varying percentages of circulating HbF-containing RBCs (% F cells). Steinberg et al. (2014) proposed that an individual HbF concentration per cell (iHbF) above 10pg inhibits the polymerization of HbS, so the development of precise methods to quantify iHbF and the percentage of F cells may allow clinicians to use those parameters as targets to monitor patient treatment. We devised a novel procedure to very accurately measure and quantify iHbF using imaging flow cytometry (Amnis Imagestream) and investigated its correlations with clinical manifestations. Samples from 54 adult SCD patients (22 [41%] female, 39 [72%] on hydroxyurea) were used to acquire images from RBCs labeled with fluorescent anti-HbF antibody and were analyzed using IDEAS software v 6.2. Along with the hematimetric data and HPLC quantification of total HbF of each sample, we modified the formulas by Maier-Redelsperger et al. (1994) and Horiuchi et al. (1995), with minimization of interference from autofluorescence of non-F cells, correction for area and fluorescence intensity, and analyzed RBC subpopulations with varying levels of HbF expression. Statistical analysis was performed using R considering a p value <0.05 to be statistically significant. We did not find associations of iHbF with alpha thalassemia carrier state or beta globin cluster haplotypes Benin or Bantu, the most common in our population. Perpendicular cutoff correlation studies defined two patient populations: one group with lower mean iHbF (9.9pg) and lower % F cells (28.2%) and another group with a higher mean iHbF (15.8pg) and higher mean % F cells (72.5%). The latter group had a lower frequency of vaso-occlusive crises (p=0.011). That was further validated with our finding that the cutoffs of % F cells>30% and iHbF>10pg were strongly associated with lower absolute reticulocyte counts (p<0.001), LDH (p=0.002), and indirect bilirubin (p<0.001). The association between hemolysis and iHbF was further explored regarding pulmonary hypertension, showing that a value of iHbF>10pg was associated with a lower median tricuspid regurgitant jet velocity than in patients with iHbF<10pg (2.72m/s vs. 2.29m/s, p=0.046). We also found an association of a mean iHbF<8pg with the presence of sickle retinopathy (p=0.002). Patients with retinopathy had a lower mean iHbF and % F cells than those without it (7.08pg vs. 8.75pg, p=0.032; 48.5% vs. 71.0%, p=0.043, respectively), suggesting increments in iHbF and % F cells may be protective against sickle retinopathy, a complication not usually associated with high hemolytic rates. Our results suggest that a percentage of F cells above 30% along with individual RBC HbF concentration of 10pg may be protective against complications in SCD patients and, therefore, should be explored as goals for hydroxyurea therapy in this population. In addition, the data presented here suggest further studies on the efficacy of HbF induction therapy against the development of sickle retinopathy may be performed in a large population of sickle cell disease patients.

Optimizing Use of Automated Isovolemic Hemodilution Red-Cell Exchange in a Patient Cohort with Sickle Cell Disease: A Quality Improvement Intervention

Background: Red-cell exchange (RCE) is a mainstay of treatment for both acute and chronic complications of sickle cell disease (SCD). It is a resource-intensive intervention requiring transfusion of large volumes of antigen-matched red blood cells (RBC). Identifying suitable RBC units can be challenging due to variability in blood group phenotypes between patients with SCD and the donor population. This often results in use of O-negative units, which are a scarce resource. Efforts to reduce the volume of units transfused, while maintaining therapeutic efficacy is an important clinical need. Isovolemic hemodilution (IHD) prior to RCE reduces the required volume of RBCs. The aim of this project is to evaluate the effect of a change to IHD-RCE on RBC utilization in patients with SCD receiving standard RCE. Methods: All adult SCD patients receiving standard RCE at the Ottawa Hospital were identified. To safely attain a meaningful reduction in transfused RBCs, RCE treatment parameters were individualized for each patient (Table 1). Patient hematocrit was not allowed to decrease below 20% during the depletion phase, and IHD-RCE would be performed only if an estimated reduction in RBC volume of at least 200 mL was expected. Pregnant patients were excluded. Change in RCE protocol to IHD-RCE took place in January 2022. Transfusion and clinical data were obtained from databases at the Ottawa Hospital in the six months preceding and succeeding the change in RCE protocols to allow for a pre- and post-intervention comparison. Results: Thirty-four adults receiving regular RCE for SCD were identified. Twenty-two patients met criteria for a protocol change to IHD-RCE. The mean age of the IHD-RCE cohort was 31 years (SD 9.5). Males comprised 72.7% of this cohort, with the most frequent genotype of hemoglobin SS (68.2%). Over the one-year study period, 1963 RBC units were transfused: 1035 RBC units in the pre-intervention period, and 928 units in the post-intervention period, representing a reduction of 107 RBC units. 1958 (99.7%) of the RBC units transfused were transfused in the setting of RCE, with few (5 units; 0.03%) administered as simple RBC transfusions. Table 2 outlines patient outcomes during the study period. The mean number of RBC units transfused per patient in the pre- and post-intervention periods were 47 and 42.4 units, respectively. The mean number of RBC units per RCE session per patient was significantly reduced from 8.7 units in the pre-intervention period to 7.8 units in the IHD-RCE post-intervention period (mean difference: -0.9, 95% CI: -1.2 to -0.5). A total of 236 RCE sessions occurred during the study period. No difference in RCE session frequency was observed with a change to IHD-RCE during the six-month study period, nor time between RCE sessions. Therapeutic efficacy in attaining target hemoglobin S levels was not affected by the change to IHD-RCE. No adverse patient safety signals were observed during the IHD-RCE sessions to date. Conclusions: This study demonstrates that IHD-RCE, compared to standard RCE, substantially reduces RBC utilization. A total of 107 RBC units were conserved in our patient cohort of 22 chronic RCE patients directly from the transition to IHD-RCE from standard RCE. Based on local RBC per unit costs, this corresponds to an annualized saving of $95,444 CAD. With pressure on blood banks to provide appropriately matched units, and risks of alloimmunization and delayed hemolytic transfusion reactions amongst chronically transfused SCD patients, increased uptake of IHD-RCE should be considered for SCD patients on chronic RCE. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Are Women at High Risk of Complications from Sickle Cell Disease: Insights from National Database Analysis

Introduction: Published data reporting gender-related differences in outcomes from sickle cell disease (SCD) is scarce, consisting of small single-center studies. Therefore, using a large sample size from a nationally representative database, we looked into the effect of gender on outcomes from SCD. Methods: We investigated the National Inpatient Sample 2019 using International Classification of Diseases-10 (ICD-10) codes to include adult SCD patients. Morbidity, disease complication, and resource utilization were compared, stratified by patients' gender. Analyses were performed using STATA (version 14.2), considering 2-sided P< 0.05 as statistically significant. Proportions were compared using Fisher exact test and continuous variables using the Student's t-test. Confounding variables were adjusted using multivariate logistic and linear regression analyses. Results: A total of 97,244 patients were included (mean age 34.61 years, 57.26% females). Female patients had 24% lower odds of acute chest syndrome on presentation (Adjusted odds ratio (aOR) 0.76, 95% confidence interval (CI): 0.64 - 0.91, P<0.01). The rates of splenic sequestration crisis, posterior reversible encephalopathy syndrome, myocardial infarction, and gallbladder stones were comparable between the two groups. Males had higher odds of developing acute kidney injury during hospitalization (aOR 0.80, 95% CI: 0.70 - 0.92, P<0.01), but the rates of in-hospital mortality and other morbidity markers were not different between the two groups. Packed Red Blood Cell (pRBC) transfusion, total hospital costs, and length of stay were not statistically different between males and females. Discussion: Using a large sample size, we found that females are not at high risk of SCD complications or adverse hospitalization outcomes. Male patients have a higher risk of presenting with acute chest syndrome and developing acute kidney injury. This could be due to the estrogen protective effect or other factors. Despite menstrual losses, females did not have significantly higher pRBC transfusions or lower secondary hemochromatosis. Our study showed that gender does not represent an indicator of morbidity and mortality in SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Cognitive Screening in Adults with Sickle Cell Disease: Prospective Validation of the Rowland Universal Dementia Assessment Scale

Background: Adults with sickle cell disease (SCD) are at increased risk of early cognitive decline. The American Society of Hematology recommends surveillance for cognitive impairment. However, optimal screening strategies in this population have not been established. The RUDAS (Rowland Universal Dementia Assessment Scale) is a short screening questionnaire developed for use in culturally diverse patient populations. In adults with SCD, it is less biased by educational attainment than the Montreal Cognitive Assessment (MoCA). Hypothesis: We hypothesized that the RUDAS is a valid tool to predict neurocognitive disorder (NCD) in adults with SCD. Aims: 1. Describe trends in RUDAS scores during long-term cognitive surveillance; 2. Evaluate the ability of RUDAS scores to predict the diagnosis of NCD. Method: A retrospective study was conducted. All patients who had undergone cognitive screening with RUDAS in 2018 and repeat testing as part of routine surveillance in 2021-2022 were identified. Starting in 2021, all adults with SCD are assessed by a multidisciplinary team (neurologist, hematologist, neuropsychologist) for neurocognitive screening and assessment. RUDAS was administered and scored as previously described (Forté et al, JAMA Net Open 2021). A clinical diagnosis of NCD was established by a neurologist and/or neuropsychologist. Repeated measure t-test was performed to compare RUDAS trends over time. Standard t-test was used to compare RUDAS between a priori defined subgroups (with and without NCD). Positive predictive values (PPV) were calculated. Results: From an initial assessment of 92 patients, 28 adult SCD patients met the inclusion criteria. The median age was 39 years [range: 24-65], 16 (57%) were female and the median educational level was 14 years [range: 10-18]. Genotype distribution was 18 (64%) with the SS or Sβ0-thalassemia genotype and 10 (36%) with the SC or Sβ+-thalassemia genotype. None of the patients had an established diagnosis of NCD, and 5 (18%) had a prior history of stroke. The mean (±standard deviation (SD)) RUDAS scores were 26.7±2.0 in 2018 and 27.3±2.7 in 2021-2022. Overall, the scores did not significantly change over time (+0.6±2.8, paired t-test P=0.3). In table 1, we present the results of the subgroup analysis according to NCD diagnosis. In those in whom a diagnosis of NCD was established in 2021-2022, RUDAS score declined by -0.9±2.8 points (P=0.3). In those not meeting the criteria for NCD, the mean change was +1.7±2.4 (P=0.01). RUDAS scores differed significantly in those with and without NCD (25.5±2.8 and 28.6±1.5, P<0.001). RUDAS scores <28 and even more significantly those <23 were highly predictive of a diagnosis of NCD (PPV=86% and 100%, respectively, P<0.001, table 2). Conclusion: The results of our study suggest that lower RUDAS scores are associated with the diagnosis of neurocognitive disorder in adults with SCD. Prospective validation is ongoing with a larger sample size. In addition, patient characteristics will be explored as potential predictors of NCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal