Sickle Cell-related Complications Research Articles

Acute care utilization among individuals with sickle cell disease and related cardiopulmonary and renal complications.

Cardiopulmonary and renal end organ (CPR) complications are associated with early mortality among individuals with sickle cell disease (SCD). However, there is limited knowledge regarding acute care utilization for individuals with SCD and CPR complications. Our objective was to determine the prevalence of CPR complications in a state specific SCD population and compare acute care utilization among individuals with and without CPR complications. We leveraged 2017-2020 data for individuals with SCD identified by the Sickle Cell Data Collection program in Wisconsin. The prevalence of CPR complications is determined for distinct age groups. Generalized linear models adjusted for age compared the rate of acute care visits/person/year among individuals who had cardiopulmonary only, renal only, both cardiopulmonary and renal, or no CPR complications. There were 1378 individuals with SCD, 52% females, mean (SD) age 28.3 (18.5) years; 48% had at least one CPR complication during the study period. The prevalence of CPR complications was higher in adults (69%) compared to pediatric (15%) and transition (51%) groups. Individuals with SCD and cardiopulmonary complications had higher acute visit rates than those without CPR complications (5.4 (IQR 5.0-5.8) vs 2.4 (IQR 2.1-2.5), p <0.001)). Acute care visit rates were similar between individuals with SCD who had renal only complications and no CPR complications (2.7 (IQR 2.5-3.0) vs 2.4 (2.1-2.5), p = 0.24). The high acute care visit rates, especially for those with cardiopulmonary complications, warrant further investigation to understand risk factors for CPR complications, the underlying reasons and identify effective disease management strategies.

Managing sickle cell disease and related complications in pregnancy: results of an international Delphi panel

AbstractData to guide evidence-based management of pregnant people with sickle cell disease (SCD) are limited. This international Delphi panel aimed to identify consensus among multidisciplinary experts for SCD management during pregnancy. The 2-round Delphi process used questionnaires exploring 7 topics (antenatal care, hydroxyurea use, transfusion, prevention of complications, treatment of complications, delivery and follow-up, and bottlenecks and knowledge gaps) developed by a steering committee. Thirteen panelists (hematologists, physiologists, obstetricians, maternal fetal medicine, and transfusion medicine physicians) from the United States, the United Kingdom, Turkey, and France completed the first survey; 12 panelists completed the second round. Anonymized responses were collected and summarized by a contract research organization (Akkodis Belgium). Consensus and strong consensus were predefined as 75% to 90% (9-10 of 12) and >90% (≥11 of 12) of panelists, respectively, agreeing or disagreeing on a response to a predefined clinical scenario or statement. In several areas of SCD management, consensus was achieved: experts recommended performing at least monthly multidisciplinary antenatal follow-up, administering prophylactic aspirin for preeclampsia prevention between gestational weeks 12 and 36, initiating prophylactic transfusion therapy in certain cases, or choosing automated red blood cell exchange over other transfusion methods for patients with iron overload or severe acute chest syndrome. No consensus was reached on several topics including the prophylactic aspirin dose, indications for starting infection prophylaxis, routine use of prophylactic transfusions, or use of prophylactic transfusions for preventing fetal complications. These recommendations could inform clinical care for patients with SCD who are pregnant in the absence of large clinical trials involving this population; the identified knowledge gaps can orient future research.

Improving Access to Comprehensive Care for Pediatric Sickle Cell Patients through the Creation of Multispecialty Clinics

There are many barriers to health care for those in underserved populations such as the pediatric sickle cell population. Due to limitations of transportation, clinical availability, and lack of care coordination, pediatric sickle cell patients are at an increased risk of not receiving the extensive multi-subspecialty health care recommended to prevent potential sickle cell related complications that affect every organ system. To improve access to this multidisciplinary care, UPMC Children's Hospital of Pittsburgh (CHP) pediatric sickle cell program developed a multi-subspecialty collaborative clinic model to offer coordinated sickle cell and pulmonary care, which is critical for sickle cell patients due to the increased risk of pulmonary complications associated with sickle cell disease. By considering health care barriers experienced by our pediatric sickle cell population, we proposed that this coordinated subspecialty clinic model will increase compliance by offering patients and families the opportunity to receive synchronized care from two essential subspecialty groups in just one medical center trip. This increased access to preventative health care for the pediatric sickle cell population should contribute to decreased acute medical events that require critical care and other extensive resources within the health care system. Methods: Two adjacent clinic appointments within the sickle cell and pulmonology clinics were designated for sickle cell patients also requiring preventative pulmonary care to be seen consecutively by both clinical teams during the same half day (one in sickle cell clinic and one in pulmonary clinic). The effect of improving completed referrals using this multi-specialty clinic model was assessed by retrospective electronic medical record review comparing the number of pulmonology referrals made by SCD team and pulmonary visits completed pre- and post- coordinated multi-subspecialty clinic initiative. The studied time period prior to the multispecialty clinic creation was chosen to be calendar year 2019 in order to eliminate the variable of the COVID-19 pandemic affecting outpatient clinic participation. Post-intervention data were collected during calendar year 2022 soon after the creation of this multi-subspecialty initiative. Prior to the creation of this multi-subspecialty clinic model, coordinating CHP sickle cell and pulmonology care, only 24% of pediatric sickle cell patients referred for outpatient pulmonology consultation completed the clinical evaluation. Our program referred 53 of 168 total families during calendar year 2019, with only 17 patients completing their visit. Since beginning this multi-subspecialty clinic initiative, pulmonology evaluations completed by referred sickle cell patients increased to 55%. Thus, CHP's multispecialty clinic offering coordinated sickle cell and pulmonology care increased completed pulmonology referrals by 129%. Using Pearson's chi-square test to compare the relationship between the two categorical variables of prior- and post- multispecialty clinic formation with a null hypothesis of multispecialty clinics will not increase completed referrals, we found a value of 10.76, which is greater than the applied critical value of 9.21 (p=0.01). Therefore, these results are significant, and the null hypothesis was rejected. In summary, by establishing this multi-subspecialty coordinated care at CHP for our pediatric sickle cell population, our goal of improving compliance with critical preventive care was achieved. We hope that this type of intervention will enhance the quality of life for children with sickle cell disease currently, as well as contribute to better health in the patients' futures. We also predict that this improved preventive care will also contribute to decreased emergency care and extensive treatments required for patients cared by CHP. This multi-subspecialty care model also has the potential to benefit other pediatric patients with chronic diseases from underserved populations who experience similar barriers, both in CHP's Western Pennsylvania region as well as underserved populations and health care organizations beyond our region. By applying an approach to care focused on reducing health care barriers to underserved populations, impactful improvements may be seen not only in the pediatric sickle cell population, but in the health care system at large.

Characteristics and Trends of Hospitalizations for Sickle-Cell Related Complications

Introduction There are approximately 100,000 people living with sickle cell disease (SCD) in the United States. As per the Center for Disease Control estimates, almost all patients with SCD will require hospitalization more than once a year and visit the emergency department at least 2-3 times a year on average. Previous studies have shown that SCD hospitalization trends are steadily increasing in the country. In November of 2019, two new drugs, crizanlizumab (to decrease the frequency of vaso-occlusive crises) and voxelotor (to increase hemoglobin response), were approved by the Food and Drug Administration (FDA) for the treatment of sickle cell disease. Around the same time, the entire health care system experienced disruption in the form of the COVID-19 pandemic. Hence, we conducted this retrospective study to assess SCD hospitalization trends from 2016-2020 and stratified them across various demographic factors to analyze the underlying causes. Methods We conducted a retrospective study from the National Inpatient Sample (NIS), which is a large all-payer database created by the Health Care Cost and Utilization Project (HCUP). We included all adult patients with a diagnosis of SCD (HbSS, HbSC, Sickle/b thal, and other variants) and identified their trends of hospitalizations for various SCD-related complications like vaso-occlusive crises, heart failure exacerbation, acute kidney injury, stroke, sepsis with and without septic shock, bacteremia, pneumonia, osteomyelitis, acute chest syndrome, splenic sequestration, and priapism. We then did a linear-to-linear analysis and ANOVA test to stratify these trends across various age, gender, income, and location groups. SPSS was used for the statistical analysis. Results Our study included a total of 19,250 patients who had at least one admission for sickle cell-related complications during 2016-2020. The average number of admissions for sickle cell pain crisis steadily increased from 10.2 per 100,000 in 2016 to 14.7 in 2019 and then decreased to 13.9 in 2020. Priapism steadily declined from 2.3% in 2016 to 1.4% in 2020 (p&amp;lt;0.001). Acute kidney injury complicated 4.9% of admissions in 2016 and steadily rose to 5.2% of admissions in 2020 (p = 0.88). Admissions complicated by bacteremia peaked in 2017 (0.9%) but have since been on a decline (0.5% in 2020) (p-0.02). Admissions complicated by pneumonia showed a steady decline from 6% in 2016 to 4.3% in 2020 (p&amp;lt;0.001). Admissions with osteomyelitis, splenic sequestration, acute chest syndrome, heart failure exacerbation, stroke, and sepsis complicated &amp;lt;1% of all admissions and were not statistically relevant. When stratified by age, it was noted that the age group of 18-39 had the most admissions. Females consistently had more admissions than males. Medicaid was the predominant insurance among all the admissions, followed by Medicare. Around 50% of the patients admitted for SCD-related complications were in the 0-25th percentile of median household income quartiles. The majority of admissions were seen in urban teaching hospitals. The majority of these admissions were also seen in the Southern regions. Conclusion Our results show that female patients in the age group 18-39 years, those covered by Medicaid and Medicare, and those in lower income quartiles comprised the majority of admissions for SCD-related complications. This demonstrates disparities in SCD care, wherein patients in lower socio-economic strata may not have access to newer advances in SCD treatment. Although it is optimistic to note that admissions for pain crises had a significant decline from 2019-2020, it remains to be seen whether these numbers are due to new therapies or due to the disruption of healthcare services caused by the pandemic. Analyzing more long-term trends after the year 2020 will help us understand this impact. The overall trend of infections and sepsis has been low, likely due to widespread vaccinations and early antibiotic treatments. It is interesting to note that although there was a downtrend for the majority of SCD complications, the incidence of AKI during admissions is steadily rising, validating the need to focus more on renal care in sickle cell patients.

Opening a Crack in the Door: An Interview with Haydar Frangoul

Opening a Crack in the Door: An Interview with Haydar Frangoul

Clinical Course and Outcomes in Older Patients with Sickle Cell Disease at a Community Hospital

As life expectancy improves in Sickle Cell Disease (SCD), older patients acquire age-related co-morbid conditions that impact their quality of life. In addition, they continue to suffer from sickle-cell related organ dysfunction. In this retrospective analysis of SCD patients age ≥40 years, we compared rates of hospitalization, treatments utilized and prevalence of co-morbid conditions in the common sickle cell genotypes. We conducted a retrospective study of patients with SCD, aged 40 years and older who were enrolled in the sickle cell clinic at our institution. Electronic health records over an 11-year period from 2011 to 2021 were reviewed for demographics, clinical and laboratory data and rates of hospitalization for acute sickle cell vaso-occlusive events. We utilized a feature of our electronic health record to also review hospitalization data from other hospitals in our region. We identified 64 patients aged ≥40 years with SCD who followed in our clinic. The median age was 50.6 years (range 40 to 89 years). There was a predominance of female patients (75%). Ninety-two percent of the study patients were between 40 to 69 years, with 5 patients (8%) aged ≥70 years. Patient characteristics and results are summarized in Table 1. The hospitalization rate of patients with Hemoglobin (Hb) SS genotype was significantly higher than those of other genotypes. Furthermore, patients with higher rates of hospitalization and clinic visits were more likely to be on hydroxyurea. Twenty-three percent of patients in the cohort were on disease-modifying therapies such as voxelotor, and L-glutamine. The prevalence of comorbid conditions and SCD complications are summarized in Table 2. Patients with comorbid conditions such as diabetes mellitus (DM), cancer, hypertension (HTN) and chronic kidney disease (CKD) had higher median ages than patients without those conditions. Variability in phenotypic expression of SCD has been observed even within the same genotype. We found that patients with HbSS had significantly more hospitalizations for acute sickle cell events than those with HbSC or HbSβ-thalassemia. We also observed that eleven patients (17%) had no hospitalizations for acute sickle cell events over the 11-year period reviewed. Of these, 55% were HbSC - while they had less hospitalizations for acute vaso-occlusive events, they suffered from chronic complications especially AVN. The most common co-morbid conditions identified among this older cohort of patients with SCD was HTN (45%), followed by CKD (23%), venous thromboembolism (VTE) (16%), stroke (12.5%) and cancer (12.5%). Diabetes mellitus was present in 6% of older adults in this study. Whether DM might be underdiagnosed in SCD patients due to the reduced utility of HbA1c measurements in this population is a consideration. A history of VTE was reported more commonly in HbSC genotype than HbSS or HbSβ-thalassemia. Excluding pain crises, the most common SCD-related organ complication observed among all genotypes was Acute Chest Syndrome. Patients with the HbSS genotype had higher rates of sickle cell-related complications, except for avascular necrosis (AVN) of the hip which was most common in HbSC patients. As further gains in life expectancy are made in individuals with SCD, age-related morbidities should be attentively recognized and addressed. Early recognition of any unfavorable interplay between the underlying sickling syndrome and coexisting chronic conditions should be a key component of managing older patients with SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

P1503: REAL WORLD DATA ON EFFICACY OF PHARMACEUTICAL-GRADE L-GLUTAMINE IN PREVENTING SICKLE CELL DISEASE-RELATED ACUTE COMPLICATIONS AND HEMOLYSIS IN PEDIATRIC AND ADULT PATIENTS.

Background: Oxidative stress is one of the key contributors to the pathophysiology of sickle cell disease (SCD) and related complications including acute pain (vaso-occlusive crisis or VOC), tissue ischaemia, stroke, and acute chest syndrome (ACS). L-glutamine (L-gln), a precursor of nicotinamide adenine dinucleotide (NAD), has been shown to play an important role in the regulation of oxidative stress. In the pivotal Phase 3 clinical trial, L-gln demonstrated significant reduction in VOC, hospitalizations, and ACS events compared to placebo in patients with SCD, with or without hydroxyurea (HU) use, over a 48-week period. In September 2021, a re-analysis of the Phase 3 trial data revealed that L-gln decreased the number of VOCs by 45%. Aims: To confirm the efficacy on clinical observations and hemolysis markers of oral therapy with pharmaceutical-grade L-gln in pediatric and adult patients with SCD at follow-up time points of 24, 48 and 72 weeks. Methods: In the observational study conducted from October 2019 through April 2021, 19 patients (4 patients from Qatar and 15 patients from French Guiana) were treated with L-gln (0.3mg/kg) twice daily. Laboratory parameters (hemoglobin (Hb) levels, hematocrit, WBC counts, reticulocyte counts, and LDH levels) were measured at baseline and follow-up time points. Clinical parameters (number of VOCs, hospitalizations, days hospitalized, ACS events, and blood transfusions) were documented for the year prior to treatment initiation as baseline values. These parameters were also collected at 24, 48, and 72 weeks from treatment initiation. Adverse events (AEs) were also collected during the treatment period. The data values at 24, 48, and 72 weeks have been annualized. Statistical analysis was performed using MedCalc 20.015. Results: Compared to baseline, patients had significantly fewer number of VOCs at 24, 48, and 72 weeks following L-gln therapy (median change from 3.0 to 0;p<0.00001). Compared to baseline, there were fewer hospitalizations (median change from 3.0 to 0;p<0.00001) and patients spent fewer days in hospital (median change from 15.0 to 0;p<0.00001). Furthermore, at 24, 48, and 72 weeks, the number of blood transfusions was considerably lower than at baseline (median, from 3.0 to 0.0;p<0.00001). Following treatment with L-gln, the mean Hb level increased significantly from baseline to 72 weeks (8.2 to 8.8 g/dL;p<0.001) with peak mean increase from baseline of 11.2% at 48 weeks. A similar increasing trend was observed for hematocrit proportions from baseline to 72 weeks (24% to 27%;p<0.001) with highest mean improvement from baseline of 15.5% at 48 weeks. Conversely, mean reticulocyte counts and LDH levels were significantly reduced at follow-up time points compared to baseline (p=0.003 and p<0.001, respectively). Image:Summary/Conclusion: This study demonstrated for the first time that L-gln therapy in SCD patients from Qatar and French Guiana resulted in significant improvements in clinical outcomes (number of VOCs, number and duration of hospitalizations, and number of blood transfusions) accompanied by a noteworthy increase in Hb levels and a reduction in markers of hemolysis (reticulocyte counts and LDH levels). Moreover, while 11 ACS events were reported the year before starting L-gln, only 2 ACS events occrred after 12 months of initiation of L-gln. Treatment with L-gln resulted in clinically significant outcomes combined with significant improvement of the hemolysis parameters from baseline through 72 weeks suggesting sustained long-term efficacy. Only a few number of AEs occurred and were mild. No compliance issue was reported.

A critical evaluation of crizanlizumab for the treatment of sickle cell disease

ABSTRACT Introduction P-selectin is a key adhesion molecule in the pathogenesis of sickle cell disease, including acute painful event(s). Many of the mediators activated in prototypical pain crisis are also involved in other complications seen in this population. Crizanlizumab is a monoclonal antibody approved in the US in 2019 for patients of all genotypes of sickle cell disease. By blocking P-selectin, it effectively prevents acute painful event(s) and has a manageable safety profile. Areas covered In this review, we provide an overview of the (i) biology of P-selectin in sickle cell disease, (ii) various agents inhibiting P-selectin, (iii) pharmacology of crizanlizumab, (iv) preclinical and clinical data on crizanlizumab, and (v) its potential for other indications, ongoing studies, regulatory status, and cost issues. Further, we describe its position among other approved agents in sickle cell disease and project future directions as well. Expert opinion Crizanlizumab holds great promise in modulating the natural history of sickle cell disease and may have pleotropic effects. Studies are ongoing to define its role in preventing other sickle cell-related complications, non-sickle cell inflammatory states, and thrombotic disorders.

Impact of Alloimmunization in Patients with Sickle Cell Disease

INTRODUCTIONBlood transfusion is an essential therapeutic and prophylactic component in the management of sickle cell disease (SCD) and associated complications. Prolonged transfusion therapy can lead to the development of antibodies to the donor's RBC antigens (alloimmunization), causing complications such as delayed hemolytic transfusion reactions, hyperhemolysis, worsening vaso-occlusive episodes, and end-organ damage. There have been only a few case series highlighting the impact of RBC alloimmunization on SCD morbidity and mortality, proposing a pathway involving RBC alloimmunization and decreased survival associated with hemolytic reactions or difficulty obtaining compatible blood when needed. However, apart from the consequences of iron overload, there is no long-term data for alloimmunization highlighting the clinical consequences, multiorgan damage, or associated morbidity in sickle cell patients.AIMThe primary aim is to investigate the incidence of alloimmunization in SCD patients in an academic health system. The secondary aim is to elucidate the differences in demographics, frequency of vaso-occlusive crisis, end-organ damage, and inflammatory markers between alloimmunized and non-alloimmunized SCD patients.METHODSWe conducted a retrospective multicentric descriptive study, including all sickle cell patients treated in an academic health system from January 1st, 2009, to December 31st, 2020, in Maryland, Virginia, and Washington, DC. An exemption from the Institutional Review Board for obtaining individual subjects' consent was procured. Patients included in the study were older than 18 years and diagnosed with sickle cell disease. Patients who did not have sickle cell disease were excluded from the study. Statistical analysis was reported using means for descriptive data, t-test for continuous variables, and chi-square for categorical variables.RESULTSA total of 94 patients with sickle cell disease were included in the study. Of these, 24 (25.5%) patients were found to have alloimmunization, whereas 70 (74.4%) patients did not. Of the alloimmunized patients, the average age, BMI and BSA were 30.15 years (p=0.037), 23.15 kg/m2 (p=0.040), and 1.65 m2 (p=0.003) compared to 37.07 years, 26.17 kg/m2 and, 1.84 m2 respectively among the non-alloimmunized group. 83% of the alloimmunized patients had sickle cell anemia (Hb SS), and 17% had a sickle thalassemia phenotype (p=0.005). A lower baseline hemoglobin (Hb) value of 8.01 g/dL was seen among alloimmunized patients compared to a higher Hb value of 9.63 g/dL (p=0.001) among the non-alloimmunized. Alloimmunized patients had an average of 5.55 alloantibodies. The average number of vaso-occlusive crises per year and related hospitalizations was statistically significantly higher in the alloimmunized group with 4.82 and 3.78, respectively, compared to 2.34 (p=0.035) 1.01 (p=0.0005) in the non-alloimmunized group. Similarly, the incidence of other sickle cell-related complications were higher among the alloimmunized patients, such as priapism (29% vs. 9%; p=0.0139), pulmonary hypertension (38% vs. 9%; p=0.0038) with no statistical difference in the iron overload (25% vs. 11%; p=0.150) or ferritin levels (. 83% of alloimmunized patients had a history of narcotic use vs. 34% among the non-alloimmunized (p=0.0001). Higher use of disease-modifying therapies including hydroxyurea (71% vs. 31%; p=0.0009) and voxelotor (13%vs0; p=0.0029), were also seen among alloimmunized patients. While no statistically significant difference was seen in the mean number of lifetime transfusions, there was a difference in the mean number of lifetime exchanges (3.67 vs. 0.0; p=0.0208).CONCLUSIONThe prevalence of alloimmunization in sickle cell patients in our study population (25.5%) was higher than in the literature (7- 59%) and the general population (2%). An increase in alloimmunization was associated with an increased number of exchanges but not with simple transfusions. Independent from the iron overload, alloimmunization was associated with increasing end-organ damage and sickle cell complications such as priapism, pulmonary hypertension. Strategies to decrease alloimmunization are needed to prevent these complications. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pregnancy Outcomes in Women with Sickle Cell Disease in California: A Retrospective Cohort Study

▪Background:Women with sickle cell disease (SCD) are at high risk for obstetrical and SCD-related complications throughout pregnancy. Given the dearth of recent population-based studies on female reproductive health in SCD, we used hospitalization data from the socio-economically diverse state of California to describe peripartum outcomes in women with SCD.Methods:For our retrospective cohort study, we identified females with SCD who were either evaluated in the emergency department (ED) or hospitalized between the ages of 10-45 years from California's patient discharge dataset (1991-2016). We defined SCD severity by frequency of utilization with severe disease requiring an average of ≥ 3 hospitalizations and/or ED visits per year, and less severe with an annual rate of < 3 acute care visits. We used ICD-9/10-CM codes to identify all deliveries, and categorized pregnancy outcomes as either incomplete (hydatidiform mole, elective termination, miscarriage, and ectopic pregnancies) or delivery (live or stillbirths). We defined race/ethnicity as Black (or African American) vs. non-Black and quantified the total number of pregnancies for each patient. We described delivery age, mode (C-section vs. vaginal), outcome (live vs. stillbirth), median length of stay (LOS), and maternal mortality for the first in-hospital delivery.Results:Our cohort comprised 3,089 females with SCD of childbearing age, with a median follow-up of 11 years. Of the 1,108 (35.9%) women with at least one pregnancy, 1,000 (90.3%) were Black and 591 (53.3%) had severe SCD. Overall, we observed 2,330 pregnancies; of the 1,864 (80%) deliveries , 45% occurred via C-section (Figure 1). When we restricted our analysis to first deliveries only, 346 (36.0%) occurred in women ages 20-24 years; the next highest proportion of deliveries (23.4%) was in adolescents ages 15-19 years (Figure 2). Only 5.5% of deliveries occurred in women ≥ 35 years old. One hundred seventy-two (15.5%) first pregnancies were incomplete (Table 1), primarily due to miscarriage (59.3%). Of the women with incomplete first pregnancies, 69.2% had severe SCD; in contrast, 50.4% had severe SCD in the first delivered pregnancies' subset. Of the 936 first deliveries, 41.5% were by C-section with a median LOS of 5 days, compared with 3 days for those who delivered vaginally. Twenty-two first deliveries (2.4%) were stillbirth for a rate of 24.9 stillbirths per 1000 deliveries. Of the 862 live births, 5 women died, which resulted in an inpatient maternal mortality rate of 580.1 per 100,000 live births.DiscussionPregnant women with SCD first delivered in the hospital at a mean age of 24.1 years, which is younger than the US national mean of 26.8 years (all races) and 24.9 years (Black), based on 2017 maternal health data from the Centers for Disease Control and Prevention (CDC). We attribute this age difference to the higher proportion of first deliveries in adolescents with SCD coupled with the trend towards older age of first delivery in the general population. For first deliveries, 41.5% of women with SCD underwent a C-section, compared with a 2013 national average of 22.8% (all races) and 25.7% (Black) in primigravid women in the US. Stillbirths in our SCD cohort surpassed the 2014 national rates of 5.9 (all races) and 10.3 (Black) stillbirths per 1000 deliveries. Lastly, the inpatient maternal mortality rate in women with SCD, while based only on 5 deaths, far exceeds the 2014-2017 US maternal mortality rates of 17.3 (all races) and 41.7 (Black) deaths per 100,000 live births.Limitations include the lack of outpatient data, which likely resulted in an underestimation of the total number of pregnancies. Maternal mortality rates from the CDC cover death up to 12 months postpartum, so a comparable mortality rate for women with SCD might be higher. The striking disparities in outcomes in our study cohort, compared to national averages, suggests notable deficits in the optimal management of pregnancy in SCD. Analyses are ongoing to determine the effect of pregnancy on sickle-cell related complications, to evaluate the frequency of peripartum complications in women with SCD (e.g., venous thromboembolism, preeclampsia, and post-partum hemorrhage), and to compare rates of obstetrical complications in SCD vs non-SCD women, adjusted for social determinants of health. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Scalp Swelling and Headache in a 12-year-old Boy

1. Kathryn Westphal, MD* 2. Respicius Bakalemwa, MD† 3. Elizabeth Groothuis, MD, MPH* 1. *Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 2. †Department of Pediatrics, Bugando Medical Centre, Mwanza, Tanzania A 12-year-old boy with sickle cell disease (SCD) is admitted to a hospital in Mwanza, Tanzania, with acute onset of periorbital and scalp swelling. Associated symptoms include fever, headache, difficulty breathing, and back pain. Because resources in sub-Saharan Africa are limited, access to comprehensive care for patients with SCD is variable. The general principles of management focus on early diagnosis, parental education, prevention of infection with vaccinations and prophylactic medications, prompt treatment of infection and pain, the use of hydroxyurea for stroke prevention, and blood transfusions for life-threatening anemia. This patient has a known diagnosis of SCD but has infrequent pain episodes and no previous transfusions. He is not receiving hydroxyurea or prophylaxis against bacterial infections or malaria. He has no history of stroke and no known head trauma. On presentation he is afebrile and his heart rate is 120 beats/min, respiratory rate is 40 breaths/min, and blood pressure is 105/75 mm Hg. His oxygen saturation is 92% in room air. Physical examination is significant for pallor, periorbital edema, scalp edema, dyspnea without adventitious lung sounds, and splenomegaly with diffuse abdominal tenderness. His scalp edema is fluctuant and extends posteriorly from the periorbital region, encompassing the entire scalp. Swelling is most prominent in the frontal and parietal areas. The overlying skin is nonerythematous and nontender but is warm to the touch. His neurologic examination has no focal findings, although generally he appears tired. Initial laboratory results demonstrate a white blood cell count of 84,000/μL (84×109/L) with a lymphocytic predominance (57%), a hemoglobin level of …

Outcomes of Red Cell Exchange in Pregnant Patients with Sickle Cell Disease: A Case Series

Background: Pregnant patients with sickle cell disease (SCD) have higher morbidity compared to patients without SCD. SCD during pregnancy can increase the risk of fetal and obstetrical complications including preterm birth, preeclampsia, and others. Moreover, during pregnancy SCD can become more severe resulting in more sickle cell vasoocclusive crisis. Prophylactic transfusion during pregnancy has been used in practice to reduce sickle cell pain crisis since hydroxyurea is contraindicated during pregnancy. However, using prophylactic red blood cell exchange (RBCX) has been a controversial topic. In this study, we aim to evaluate the outcomes of red blood cell exchange in pregnant patients with SCD Methods: This is a retrospective study. We evaluated the charts of three pregnant patients who were enrolled in the chronic RBCX program at the University of Nebraska Medical Center at the time of their pregnancy. Data was collected to assess the sickle cell disease related complications during pregnancy, outcomes of pregnancy, and safety of the red blood cell exchange. Results: A total of 19 exchange procedures were performed for three pregnant patients while being enrolled in the chronic red blood cell exchange program. Patients demographic is summarized in table 1. The indication for enrollment in the red cell exchange program were recurrent vasooclussive crisis in patient 1 and 3, avascular necrosis in patient 2. The pregnancies were uncomplicated except for preeclampsia in the third patient resulting on early delivery. Overall, the three patients had less frequent visits to the emergency room for sickle cell related complications after starting apheresis and during pregnancy (Figure 1). We believe that the modest improvement that was noticed for the third patient was due to late enrollment in the exchange transfusion program and her older age compared to the two other patients Conclusion: Our study shows that red blood cell exchange for SCD patients during pregnancy can be safe, feasible, and can reduce the visits to the emergency room due to SCD related complication. Further larger studies are warranted to confirm this. Disclosures Gundabolu: BioMarin:Consultancy;Bristol Myers Squibb pharmaceuticals:Consultancy.

Sickle Cell-Related Complications in Patients Undergoing Cardiopulmonary Bypass.

We aimed to describe our experience with patients with sickle cell trait (SCT) and undergoing surgery on cardiopulmonary bypass (CPB). Data on all patients with SCT or sickle-α thalassemia who underwent surgery on CPB were collected (1996-2017). Overall, 46 patients were included, 37 (80%) had SCT and 9 (20%) had sickle-α thalassemia. A total of 4 (9%) developed a potential sickle cell-related complication. Patients with sickle cell-related complications were significantly older (median 14 years vs 14 months, P = .037) and heavier (median 54 kg vs 9 kg, P = .041). Complications occurred, although without statistical significance, in patients who underwent longer median CPB times (249 minutes vs 137 minutes, P = .069), lower median temperature (31.7 °C vs 33.3 °C, P = .094), and a higher percentage underwent deep hypothermic circulatory arrest (50% vs 7%, P = .053). A total of 30 (65%) patients underwent exchange transfusion (ET) pre-bypass. Patients who underwent ET were significantly older (median 4 years vs 7 months, P = .003) and heavier (median 16 kg vs 6 kg, P = .015) than patients who did not undergo ET. The incidence of complications was comparable between patients who underwent ET (10%) and those who did not (6%). In this retrospective, single-center study, it has been shown that cardiac surgery requiring CPB in patients with SCT and sickle-α thalassemia had a low risk for sickle cell-associated complications. In this cohort of patients, older age, longer CPB times, lower median temperature, and the utilization of deep hypothermic circulatory arrest appear to play an important role in the development of complications.

Preserved efficiency of sickle cell disease placentas despite altered morphology and function

IntroductionPregnant women with sickle cell disease (SCD) are at high risk for sickle cell-related complications, obstetrical complications, and perinatal morbidity. Chronic inflammation and the proangiogenic environment associated with SCD have been associated with endothelial damage.It is unknown whether SCD complications could be associated with placental dysfunction or abnormal placental morphology. Moreover, circulating angiogenic factors in pregnant women with SCD are unexplored. MethodsClinical records, placental and blood samples were collected at term delivery for 21 pregnant patients with SCD and 19 HbAA pregnant controls with adapted to gestational age birth weight newborns. Histological and stereological analyses and scanning electron microscopy (SEM) of the placenta, and PlGF and sFlt1 measurements in blood were performed. ResultsIn the SCD group, the parenchyma-forming villi of placentas were thinner than in controls, and increased fibrinoid necrosis and an overabundance of syncytial knots were seen. SEM revealed elongated intermediate villous endings with a reduction in the number of terminal villi compared to controls, indicating a significant branching defect in SCD placentas. Finally, SCD patients had an imbalance in the angiogenic ratio of sFlt1/PlGF (p = 0.008) with a drop of PlGF concentrations. DiscussionWe evidence for the first time both abnormal placenta morphology and altered sFlt1/PlGF ratio in SCD patients, uncorrelated with maintained placental efficiency and fetal growth.

Preoperative blood transfusions for sickle cell disease.

Preoperative blood transfusions for sickle cell disease.

A patient-centered medical home model for comprehensive sickle cell care in infants and young children.

The patient-centered medical home (PCMH) has been proposed as a model for comprehensive care coordination and delivery for children with sickle cell disease (SCD), yet little is known regarding the implementation of PCMH core concepts on adherence to preventative care measures, health care utilization, and parent satisfaction. We implemented the newborn cohort clinic (NCC) to explore the application of the PCMH model for infants and children with SCD from birth to age 3years in 2011. In July 2017, we conducted a retrospective chart review to evaluate subjects currently or previously followed in the clinic. We surveyed parents in the NCC to assess their satisfaction with their experience. A total of 112 patients have been managed in the NCC. All patients received penicillin prophylaxis, while 70% and 73% of patients, respectively, received the 23-valent pneumococcal vaccine and an initial transcranial Doppler by age 36months. Most (92 of 112) of the subjects utilized the emergency department (569 encounters), with 86% of encounters for fever or other sickle cell-related complications. The majority of parents indicated satisfaction with the clinic, with 71% saying clinic providers always or usually spent enough time with their child, listened carefully to them (81%) and were sensitive to family values and customs (77%). A comprehensive sickle cell clinic as a component of a PCMH is feasible and can achieve high levels of preventative care. Parents are largely satisfied with this model of care.

Burden of Sickle Cell Disease in Ghana: The Korle-Bu Experience.

In Africa, sickle cell disease (SCD) is a major public health problem with over 200,000 babies born per year. In Ghana, approximately 15,000 (2%) of Ghanaian newborns are diagnosed with SCD annually. A retrospective review of medical records of all SCD patients aged 13 years and above, who presented to the sickle cell clinic at Ghana Institute of Clinical Genetics (GICG), Korle-Bu, from 1st January 2013 to 31st December 2014, was carried out, using a data abstraction instrument to document their phenotypes, demographics, attendance/clinic visits, pattern of attendance, and common complications seen. During the period under review 5,451 patients were seen at the GICG, with 20,788 clinic visits. The phenotypes were HbSS (55.7%) and HbSC (39.6%) with other sickle cell phenotypes (4.7%). Out of the 20,788 clinic visits, outpatient visits were 15,802 (76%), and urgent care visits were 4,986 (24%), out of which 128 (2.6%) patients were admitted to the Teaching Hospital for further management of their acute complications. There were 904 patient referrals (out of 5,451 patients) for specialist care; the 3 specialties that had the most referrals were Obstetrics and Gynaecology (168 patients), Orthopaedics (150 patients), and Ophthalmology (143 patients). In 2014, complications seen at KBTH included 53 patients with avascular necrosis (AVN) and 61 patients with chronic leg ulcers. Our centre has a large number of patients living with sickle cell disease. From our experience, early recognition and referral of sickle cell related complications can reduce morbidity and mortality associated with this disease. A multidisciplinary approach to care of SCD patients is therefore important.

High Incidence and Recurrence Rate of Venous Thromboembolic Events in Patients with Sickle Cell Disease

Introduction:Sickle cell disease (SCD) is characterized by chronic hemolytic anemia and chronic inflammation resulting in endothelial damage, neutrophil and platelet activation, enhanced cell adhesion and coagulation activation. Due to these conditions, sickle cell disease is considered to be a procoagulant condition. However, limited studies have evaluated the incidence of thrombosis in sickle cell disease and clinical risk factors for thrombosis are not clear. Here we present a retrospective cohort study to determine the incidence of VTE in a well characterized cohort of adult sickle cell patients.The aim of the study was to assess the cumulative incidence of venous thromboembolic events in patients with SCD and to relate this complication with clinical risk factors, genotype, organ damage and laboratory parameters.Methods:All patients with SCD (HbSS, HbSC, HbSβ0 thalassemia, HbSβ+ thalassemia) of ≥ 18 years in a tertiary clinic for SCD at the Amsterdam University Medical Center in the Netherlands were eligible for the study. Patients with a history of prior VTE or VTE or VTE at first presentation were excluded. Patients were divided into a subgroups with a severe genotype (HbSS/HbSβ0 thalassemia) and a mild genotype (HbSC/HbSβ+ thalassemia). Hospital electronic records were analyzed for occurrences of deep vein thrombosis (DVT) or pulmonary embolism (PE) objectified with diagnostic tests (ultrasound, high probability ventilation/perfusion scan or CT angiography). All sickle cell related complications, organ damage and clinical risk factors at the time of the VTE were scored. General laboratory parameters were gathered from patient records in steady state condition.Results:In total 228 patients were included in the study with a mean age of 24 ± 10 years at the start of follow up years and a total follow up of 1548 patient years. Median follow up was 5 years (IQR 2-10). Twenty-one patients suffered one or more VTE episodes (9.2%), resulting in an incidence rate in the entire cohort of 13.6 VTE events per 1000 patient years (95%Cl 9.7-22.0). We recorded 8 recurrences of VTE in 5 patients (1 patient suffered two VTE recurrences, and 1 patient had three VTE recurrences) with a median time to recurrence of 3 years (IQR 1-4). Mean age at the time of first VTE was 29 years. The first VTE episodes consisted of an isolated DVT of the leg/arm in 8/21 patients, an isolated PE in 10/21 patients, and a combined DVT and PE in 3/21 patients. Of these first VTE episodes 9/21 (43%) were found to be idiopathic, 5/21 (24%) occurred during oral contraceptive use and 7/21 (33%) were provoked by recent surgical procedure/hospital admission/central venous catheter. VTE was significantly associated with a previous history of acute chest syndrome (ACS) (OR 10.6 [3.3 - 46.6] P<.001), avascular necrosis (AVN) (OR 5.6 [2.1 - 15.0] P <.001) and a ferritin level >1000 μg/L (OR 3.8 [1.4 - 10.2] P=0.023). No significant association with other forms of organ damage was found. Patients with a severe genotype had a higher incidence of VTE than patients with a mild genotype (11.4% versus 5.6%). In the severe genotype subgroup, lower median HbF levels correlated with an increased risk of VTE (P <.005). Ten patients died during follow-up at a mean age of 40 ± 16 years.Conclusion:Sickle cell patients have a remarkably high incidence rate of VTE (13.6 events per 1000 patients years) with a high recurrence rate (23.8%). This confirms the hypercoagulable state of patients with SCD. Sickle cell related complications like ACS and AVN were associated with VTE. Given the high incidence and recurrence rate, awareness for VTE in SCD patients is warranted and long term anticoagulation may be indicated. DisclosuresNo relevant conflicts of interest to declare.

Outpatient Healthcare Utilization and Rates of Co-Management Among Medicaid Patients with Sickle Cell Disease in North Carolina

Introduction: Sickle cell disease (SCD) is a complex disease for which pain is the hallmark, often results in end-organ failure, and is associated with early death. Primary care providers (PCP's), hematologists, and co-management between PCP's and hematologists are necessary to facilitate optimal patient outcomes. Due to the wide array of sickle cell related complications, multiple specialists are required to manage patients with SCD. We report outpatient visits per provider specialty type and co-management, for persons with SCD enrolled in Medicaid during a 12-month period in North Carolina.Methods: Medicaid claims data from North Carolina for patients with a diagnosis of SCD (ICD 9 CM codes: 282.6x, ICD 10 CM codes: D57.0x, D57.1, D57.2x, D57.4x, D57.8x) and at least one month of enrollment in Medicaid between March 1, 2016 and February 28, 2017 were examined. Outpatient visits were identified by the current procedural terminology (CPT) code listed on the claim. Each outpatient visit was then categorized into a specialty using the descriptions from the Medicare Provider/Supplier to Healthcare Provider Taxonomy document that matched the billing provider code and the rendering provider code listed on the claim. If the billing provider or rendering provider code was either missing or did not link to a description that was informative, then those visits were placed in the “NULL” category to signify they were unidentifiable. The “Other Specialty” category included those specialty visits that were either not historically associated with SCD care (such as infectious disease) or occurred ≤1% of all specialty visits (such as dermatology or rheumatology), and excluding SCD specialists, general nurse practitioner and physician assistant visits. Additionally, each outpatient visit type was reviewed by the team and categorized into three broad categories: PCP (including pediatrician), hematologist (including pediatric hematologists), and non-hematology specialty type. An acute care specialty visit (CPT code) occurred outside the emergency department and was defined as a non-PCP and non-hematologist visit that we were unable to further determine specialty type.A minimum of one PCP and one hematologist visit/patient during the study period was required to meet the definition of co-management. A fourth category of provider type (nurse practitioner or physician's assistant) was added whenever we were unable to determine if the NP or PA provided primary care, hematology, or other specialty care. These visits were not included in calculation of co-management. Descriptive statistics were used to report findings.Results: 2850 patients [58% female, mean (SD) age - 23 (16)] were included in the cohort. Eighty-six percent of the sample was enrolled in Medicaid for a minimum of 10 months. Table 1 reports the number of visits, and visits/patient for each category of provider type. Patients had 2.96 (SD 3.76) PCP visits per patient and only 1.28 (SD 2.49) hematology visits per patient. Although there were a large number of PCP and hematology visits overall, only 34% of the cohort met the definition for being co-managed. Table 2 reports the wide array of non-hematology specialty visits by type. On average, patients had nearly the same number of non-hematology specialty provider visits than PCP visits.Conclusions: Persons with SCD in NC had low rates of co-management and used outpatient services from a wide array of specialty providers. Importantly, hematologists had lower than expected outpatient visits and patients had a significant number of acute care outpatient visits. Navigating the large number of providers and specialists requires careful evaluation of our current model of care for treating SCD. Further efforts are required to increase co-management among complex chronic diseases such as SCD. DisclosuresShah:Novartis: Research Funding, Speakers Bureau. Tanabe:NIH and AHRQ: Research Funding; Alliant Health: Consultancy; Duke University: Employment.

Clinical and Laboratory Predictors of Frequency of Painful Crises among Sickle Cell Anaemia Patients in Nigeria.

The severity of Sickle Cell Anaemia (SCA) in terms of frequency of painful Vaso-Occlusive Crises (VOC) may be affected by clinical and haematological parameters amongst others. Elucidation of these factors in a given disease prevalent environment is necessary for prompt and effective management of patients with frequent painful VOC. This study aimed at determining the clinical and laboratory predictors of frequency of painful VOC among SCA patients in Enugu, Southeastern Nigeria. It was a cross-sectional study of 100 consecutive SCA patients receiving care at the University of Nigeria Teaching Hospital, Enugu, Nigeria between May 2012 and February 2014. The eligible patients were categorized into two groups namely; Group A and Group B. Group A/study group (severe disease) comprised SCA patients who had experienced three or more painful crises (≥3 crises) in the last one year preceding the study but, currently in steady state, while Group B/control group (mild-moderate disease), comprised SCA patients matched for age, sex, highest educational status, and occupation but who have had no painful crisis or had only one or two painful crises (0-2 crises) in the last one year preceding the study and currently in steady state. The overall mean age of the patients was 18.4±12.2 (range=2-52) years. The mean values of the haematological parameters including haemoglobin concentration, white cell count, platelet count, and neutrophil count were significantly higher in those with severe crises than mild-moderate crises (p<0.05). Sickle cell related complications including Avascular Necrosis (AVN) and leg ulcers were significantly higher in the study group than the control group (p<0.05). There was significant association between the frequency of crises and haemogblobin level, platelet and neutrophil counts and some clinical parameters: AVN, nephropathy and stroke. Future preventive interventions for reduction in frequency of crisis amongst patients with SCA could be targeted at controlling the blood levels of the identified haematological parameters.