Hydroxyurea Utilization in Nigeria, a Lesson in Public Health.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 80-80 ◽  
Author(s):  
Zakari Y. Aliyu ◽  
Aliyu Babadoko ◽  
Aisha Mamman
Keyword(s):  
Health Care ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Studies ◽  
The United States ◽  
Cell Disease ◽  
Hydroxyurea Treatment ◽  
Transfusion Requirements ◽  
The World

Abstract Hydroxyurea is a successful and cost effective drug therapy for sickle cell disease. Treatment with hydroxyurea is associated with a significant decrease in sickle cell complications, hospitalizations and transfusion requirements by about 50% and mortality reduction by 40% in clinical studies. The drug is unfortunately underutilized in sickle cell disease in the United States despite clear efficacy data and management experience. There is no data on the utilization of hydroxyurea in Africa, a part of the world with the highest global burden of sickle cell disease. We prospectively interviewed 206 consecutive adults and pediatric sickle cell patients as part of the Nigerian pulmonary hypertension screening study and reviewed over 1000 patients followed longitudinally at Ahmadu Bello university teaching hospital in Zaria, Nigeria. We also interviewed 10 hematologists (3 specialists and 7 hematologists in training) at the same university hospital. 65% of the 206 prospectively evaluated patients met the Multicenter Study of Hydroxyurea clinical indications for hydroxyurea treatment. No patient (zero percent) was on hydroxyurea therapy. All hematologists (100%) reported their discomfort with instituting hudroxyurea. Barriers to hydroxyurea utilization identified by practitioners included safety and toxicity profile (100%), patient compliance (100%), effective follow up (100%), drug availability (100%), affordability (100%) and specifically concern for reactivation of latent tuberculosis (50%) and carcinogenesis (100%) and teratogenicity (100%). Only 5% of patients had been informed of or were aware of hydroxyurea as a treatment option in sickle cell disease. Patient related barriers to hydroxyurea identified include lack of awareness (95%), cost (100%), availability (100%), need for frequent follow up (90%), pregnancy restrictions and need for concomitant contraceptive use (98%) and risk of infections (98%). Our study indicates the absolute lack of hydroxyurea utilization in a major health care center in Nigeria. Nigeria has the highest incidence of sickle cell disease in the world with about 150,000 children born with the disease annually. Sickle cell disease accounts for about 9 –16% of under-five mortality rates in the country. The sickle cell disease related morbidity, mortality and health systems financial burden remains very high in Nigeria and most of Africa. Local health care provider education and support and patient counseling and education are needed for the successful introduction of hydroxyurea in Nigeria. Clinical studies designed to assess the safety and efficacy of hydroxyurea in unique African settings is needed to facilitate the introduction and utilization of hydroxyurea in Nigeria and other parts of Africa.

The Department of Health and Human Services (DHHS) Sickle Cell Disease (SCD) Initiative: Increasing Access and Improving Care

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4834-4834
Author(s):  
Susan B. Shurin ◽  
Hani Atrash ◽  
Coleen Boyle ◽  
R. Lorraine Brown ◽  
Janet L. Collins ◽  
...  
Keyword(s):  
Health Care ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Health Care Providers ◽  
The United States ◽  
Evidence Based ◽  
Care Providers ◽  
Cell Disease ◽  
Evidence Based Guidelines ◽  
Support Research

Abstract Abstract 4834 Over the past half century, the course of sickle cell disease has been transformed in the United States through the conduct of rigorous biomedical research and broad application of the results. Universal newborn screening with comprehensive medical care has dramatically reduced death and disability in childhood, and increased the numbers of patients surviving into adulthood. However, access to health care has not kept up with the changing demographics of those affected by sickle cell disease. Health care often becomes fragmented when patients transition from pediatric to adult health care providers. Access to comprehensive care has impeded both conduct of clinical and implementation of research results. To address these needs in this changing environment, HHS Secretary Kathleen Sebelius has charged six agencies of HHS – NIH, CDC, HRSA, FDA, AHRQ and CMS – and the Offices of Minority Health and Planning and Evaluation, to improve the health of people with SCD. The agencies are coordinating their programs and collaborating with the Office of the Secretary, to achieve the following goals:create a comprehensive database of individuals with SCD to facilitate the monitoring of health outcomes and clinical research;improve the care of adults and children through development and dissemination of evidence-based guidelines, which are anticipated in Spring, 2012, with broad implementation plans;identify measures of quality of care for individuals with SCD and incorporate them into quality improvement programs at HHS;increase the availability of medical homes to improve patient access to quality primary and specialty care;provide State Medicaid officials, health care providers, patients, families and advocacy groups with information about resources related to SCD care and treatment;work with the pharmaceutical industry and academic investigators to increase the development of effective treatments for patients with SCD;support research to improve health care for people with SCD;support research to understand the clinical implications of SC trait;engage national and community-based SCD advocacy organizations and experts in ongoing discussions to ensure that issues of importance to persons affected are addressed. Organizational and strategic actions are being taken at each agency to enhance implementation of research advances; provide evidence-based guidelines to families, health care providers, and payers; facilitate new drug development; and provide public health data to impact both the health care delivery and research agendas. The enthusiastic support of the American Society of Hematology and its members is essential for long-term success of this endeavor. Disclosures: No relevant conflicts of interest to declare.

Three-Year Follow-Up of Hydroxyurea Treatment in Severely Ill Children with Sickle Cell Disease

1997 ◽  
Vol 19 (4) ◽  
pp. 313-318 ◽  
Author(s):  
M. de Montalembert ◽  
M. Belloy ◽  
F. Bernaudin ◽  
F. Gouraud ◽  
R. Capdeville ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Hydroxyurea Treatment

Hydroxyurea can eliminate transfusion requirements in children with severe β-thalassemia

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1529-1530 ◽  
Author(s):  
Mohamed Bradai ◽  
Mohand Tayeb Abad ◽  
Serge Pissard ◽  
Fatima Lamraoui ◽  
Laurent Skopinski ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Chelating Agents ◽  
Fetal Hemoglobin ◽  
Thalassemia Major ◽  
Thalassemia Intermedia ◽  
Cell Disease ◽  
Marked Elevation ◽  
Transfusion Requirements

Abstract Hydroxyurea (HU) enhances fetal hemoglobin (Hb) production. An increase in total Hb level has been repeatedly reported during HU treatment in patients with sickle cell disease and in several patients with β-thalassemia intermedia. Effects in patients with β-thalassemia major are controversial. We now report a marked elevation of total Hb levels with HU that permitted regular transfusions to be stopped in 7 children with transfusion-dependent β-thalassemia. The median follow-up was 19 ± 3 months (range, 13-21 months). We conclude that HU can eliminate transfusional needs in children with β-thalassemia major, which could be particularly useful in countries such as Algeria, where supplies of blood or chelating agents are limited.

Comparing Patterns for Transitioning the Care of Young Adults with Sickle Cell Disease Versus Hemophilia: The Toronto Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2072-2072 ◽  
Author(s):  
Ewurabena Simpson ◽  
Richard Ward ◽  
Melanie Kirby ◽  
Isaac Odame
Keyword(s):  
Health Care ◽  
Young Adults ◽  
Sickle Cell Disease ◽  
Medical Care ◽  
Disease Severity ◽  
Sickle Cell ◽  
Cell Disease ◽  
Adult Care ◽  
Effective Transfer

Abstract Abstract 2072 Background: The Hospital for Sick Children (HSC) in Toronto, Canada cares for more than 700 children with sickle cell disease (SCD), which is the largest Canadian population of children with SCD. Since 2009, the SCD Program at HSC has partnered with adult hematologists within the Red Blood Cell Disorders program at Toronto General Hospital (TGH) to develop a coordinated strategy for transitioning the care of young adults with SCD. Hemophilia is a chronic hematological condition which, like SCD, has a spectrum of disease severity that requires multidisciplinary follow up. At HSC, we care for nearly 200 patients with hemophilia A and B and have a long-established partnership with adult hematologists, which has led to an effective transfer of patients with hemophilia into adult care. In Ontario, adult health providers are remunerated according to a fee-for-service billing schedule. In contrast, pediatric subspecialists are mainly salaried under an alternate funding plan. Until 2010, adult hematologists who provided medical care for individuals with hemophilia received a significantly higher pay scale than those who cared for individuals with SCD. This was changed in July 2010 so that adult hematologists receive commensurate remuneration for services rendered for both hemophilia- and SCD-related medical care. Objectives: 1. To compare the patterns for transitioning patients of varying disease severity within the pediatric and adult SCD and hemophilia programs in Toronto, Ontario. 2. To identify barriers and enablers that have influenced the transition of young adults with SCD within a universal health care system. Methods: Data for active, transitioned and inactive patients in the HSC and TGH clinical programs are maintained in a database at HSC. These patient numbers were gathered according to sickle cell genotype. Similar data were available for hemophilia patients who were transitioned from HSC to adult care. Chi-square analyses were used to compare the proportions of patients in the sickle cell and hemophilia programs that were transitioned between 2009 and 2011. Results: Conclusion: The HSC-TGH- partnership has significantly reduced the number of youth with SCD who continue to be followed at HSC or are lost to follow up. However, a significant number of young adults within the HSC SCD program still need to be transitioned to adult care. For the sustainable expansion of this transitional care strategy, health policymakers must collaborate with tertiary and community level health care providers to develop a coordinated and distributed strategy for the effective delivery of comprehensive health care services for young adults with SCD. Disclosures: No relevant conflicts of interest to declare.

Sickle cell disease pain: II. Predicting health care use and activity level at 9-month follow-up.

1992 ◽  
Vol 60 (2) ◽  
pp. 267-273 ◽  
Author(s):  
Karen M. Gil ◽  
Mary R. Abrams ◽  
George Phillips ◽  
David A. Williams
Keyword(s):  
Health Care ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Health Care Use ◽  
Activity Level ◽  
Cell Disease

Health care utilization and expenditures for privately and publicly insured children with sickle cell disease in the United States

2009 ◽  
Vol 53 (4) ◽  
pp. 642-646 ◽  
Author(s):  
Mercy Mvundura ◽  
Djesika Amendah ◽  
Patricia L. Kavanagh ◽  
Philippa G. Sprinz ◽  
Scott D. Grosse
Keyword(s):  
United States ◽  
Health Care ◽  
Sickle Cell Disease ◽  
Health Care Utilization ◽  
Sickle Cell ◽  
The United States ◽  
Care Utilization ◽  
Cell Disease ◽  
Publicly Insured

scholarly journals Hydroxyurea to Treat Pediatric Sickle Cell Disease in Haiti - a Preliminary Report

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1313-1313
Author(s):  
Nicholas McGregor ◽  
Emmeline Lerebours ◽  
Prasad Bodas
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Laboratory Data ◽  
The United States ◽  
Western Hemisphere ◽  
Cell Disease ◽  
Open Label ◽  
Serious Adverse Events

Abstract Introduction. Haiti is the poorest nation in the Western Hemisphere, and the prevalence of sickle cell disease (SCD) in thatnation is twice that among African-Americans in the United States. Patients with SCD in Haiti have limited access to preventative care and disease management measures due to scarce healthcare resources. Hydroxyurea (HU) is a compelling option for the amelioration of complications of SCD in Haiti due to its relatively low cost, proven safety, and well-documented efficacy. Hydroxyurea programs have been implemented in India and in several African settings, however little data existto demonstrate the acceptability or feasibility of such an effort in Haiti. Study Design/Objectives. This is an open label, single arm pilot study with the primary objective of examining the acceptability and feasibility of the use of HU to treat children with SCD in an existing pediatric SCD program in Port-au-Prince, Haiti. Acceptability was defined as enrollment of a minimum of two-thirds of patients who are offered participation in the study. Feasibility was defined as two thirds of the enrolled patients being compliant with a defined minimum number of mandated study visits, lab draws, and HU doses. Secondary objectives include documenting the effect of HU on renal, hepatic, and bone marrow function as well as describing the incidence of clinical events in Haitian sickle cell patients taking HU. Methods. Patients with HbSS disease, age 2-15 years, who met minimum hematologic, renal, and hepatic parameters, were eligible for the study. Patients were approached for inclusion into the study consecutively during three separate enrollment periods from November 2015 through June 2016. The starting dose of Hydroxyurea (capsule and suspension form were available) was 20mg/kg which was increased to a maximum dose of 25mg/kg. Study visits occurred every 4 to 8 weeks at which point laboratory and clinical efficacy parameters, as well as potential adverse effects history were collected and dose modifications occurred. The study period for each patient will last 1 year. Akron Children's Hospital (ACH) IRB and the Haitian National Ethics Board approved the study. Funding for this project is provided through grants from the American Academy of Pediatrics and the ACH Foundation. Results. The study is ongoing with the enrollment period being closed as of June 2016. Forty-three patients have been enrolled, with a mean length of participation of 17.6 weeks (range 0-32 weeks).Forty-seven patients were offered participation in the study and 45 signed consent and underwent the screening process, generating an acceptability measure of 95.7%. Two out of the 45 screened patients were excluded based on results from screening labs (1 non-HbSS on confirmatory electrophoresis, 1 severe anemia) resulting in the final enrollment of 43 patients (23M:20F, mean age 9 years). Feasibility is being actively assessed.There have been no serious adverse events and no deaths. Three out of 43 enrolled patients were lost to follow-up and removed from the study due to missing 3 consecutive study visits (see figure 1). Compliance with mandated study visits was high among the enrolled patients with an attendance of 92.9% of the visits. Percent attainment of mandated laboratory tests is shown in table 1. No patients have had HU dose interruptions based on abnormal lab tests. Sixteen study patients have 6 month hematologic laboratory data available at this time: mean Hemoglobin and MCV have increased from 7.1 to 7.9g/dL and 90.6 to 107.1fL, respectively, and mean WBC and platelet count have decreased from 18.0 to 12.4(10^9/mL) and 557 to 413(10^9/mL), respectively. Conclusion. Results suggest that HU isan acceptable option for treating children with sickle cell disease in Haiti. Our preliminary data show that HU is feasible, safe, and effective in this setting. Challenges exist in ensuring reliable laboratory follow-up and will likely have to be addressed on an individual clinic and laboratory basis. Disclosures No relevant conflicts of interest to declare.

scholarly journals L-Glutamine and Crizanlizumab for Adults with Sickle Cell Disease (SCD) in Qatar: A Cost Effectiveness Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4945-4945
Author(s):  
Ahmed A Adel ◽  
Dina Abushanab ◽  
Anas Hamad ◽  
Daoud Al-Badriyeh ◽  
Mohamed A Yassin
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Acute Pain ◽  
Cost Effective ◽  
The United States ◽  
Treatment Modalities ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Hydroxyurea Treatment ◽  
Study Results

Abstract Background :Sickle cell disease (SCD) is a hereditary disease that is caused by autosomal recessive gene fault in the beta (β) allele of the hemoglobin (Hb) gene. As a result, sickled cells are characterized by easy and abnormal hemolysis with resultant varying degrees of anemia. Globally, the incidence of SCD is estimated to reach 400,000 persons per year, and in the United States alone, for example, the prevalence estimation is approximately 100,000 patients. Possible clinical presentations of SCD may come from different pathophysiologic mechanisms: the disfiguration of the RBC with subsequent loss of function can lead to vascular occlusion and a short lifetime of these RBCs that leads to hemolysis. The most severe and serious manifestation of SCD is the recurrent acute pain, or better known as vaso-occlusive crisis (VOC). Additionally, other clinical manifestations that SCD patients may show are acute complications such as acute chest syndrome (ACS), recurrent infections, kidney necrosis, and stroke. Such complications may affect multiple organs and can result in early death. Acute pain crisis is another common complication of SCD and is usually managed with pain medications, especially opioids, This is the first study to address two of novel therapies in patients with SCD in the Middle East. Our study was comprehensive in terms of outcome mostly encountered by SCD patients which is VOC and inclusivity of interventions mostly used for its management and was focused on the target population of in one of areas of high prevalence of SCD in the world. Our analysis tracked the CHEERS guidelines and checklist for reporting. To be also complete, we used only RCT evidence in our analysis. Additionally, in considering VOC, we ensured only studies with a definition compatible with that of the principal Crizanlizumab study were analyzed. Objectives: Treatment options for preventing vaso-occlusive crises (VOC) among sickle cell disease (SCD) patients are on the rise, especially if hydroxyurea treatment has failed. This economic analysis is conducted to assess the comparative clinical effectiveness, safety and acquisition cost of L-glutamine and Crizanlizumab for older adolescent and adults (≥16 years old) SCD in Qatar, with an emphasis on treatment costs and acute pain crises. Methods: We conduct a decision tree model, where we compare the clinical and economic outcomes of two novel FDA-approved medications which are available in Qatar; L-glutamine and Crizanlizumab over a time horizon of one year in a hypothetical cohort of adult SCD patients from a Qatar healthcare perspective. The main outcome is incremental cost per SCD-related acute pain crises averted. Model clinical parameters were derived from individual drug randomized trials, published literature, whereas cost parameters from Qatar healthcare payer system. A sensitivity analysis was carried out, and the study results were robust around model inputs. Costs were converted to 2020 US dollars. Results: Study results showed that both treatment modalities' costs were the main driver of this analysis, with average annual cost of the treatments per patient being $189,014 for Crizanlizumab (5mg/Kg), $143,798 Crizanlizumab (2.5mg/Kg) and $74,323 for L-glutamine. The probability of no first time SCD-related VOC averted were 0.001/year for Glutamine, 0.26/year for Crizanlizumab (5mg/Kg) and 0.34/year for Crizanlizumab (2.5mg/Kg). Lower dose Crizanlizumab (2.5mg/Kg) dominated the higher one (5mg/Kg). The ICER of Crizanlizumab (2.5mg/Kg), when compared to L-Glutamine was $81,265 per SCD-related VOC averted. When comparing Crizanlizumab (5mg/Kg) and L-Glutamine, Crizanlizumab (5mg/Kg) showed higher efficacy, yet the Crizanlizumab ICER was at $459,620 than L-glutamine. Conclusions: Crizanlizumab (2.5mg/Kg) may be cost-effective interventions yet it is not the approved dose for preventing VOC in adolescents and adults with sickle cell disease. Crizanlizumab (5mg/Kg) was more cost effective than the approved L-glutamine per SCD vaso-occlusive crisis prevented. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Perspective From the National Medical Association

PEDIATRICS ◽  
1989 ◽  
Vol 83 (5) ◽  
pp. 911-911
Author(s):  
Roselyn Payne Epps
Keyword(s):  
Sickle Cell Disease ◽  
Medical Association ◽  
Sickle Cell ◽  
Education Program ◽  
Well Being ◽  
The United States ◽  
Professional Organization ◽  
Cell Disease ◽  
National Medical

I am pleased to comment as a member of the National Medical Association, the professional organization founded in 1895, which currently represents the 14,000 black physicians practicing in the United States. Members of the National Medical Association (many of whom have been inspired by the leadership of Dr Roland B. Scott) have been and continue to be in the forefront of sickle cell disease research. Their sustained interest and that of many other colleagues has contributed to the research accomplishments we observe today. On the other hand, some physicians have been reluctant to assume a prominent role in sickle cell screening, counseling, and follow-up because of their own uncertainties and legitimate differences of opinion. During this conference, experienced and knowledgeable speakers have eloquently presented varying and sometimes divergent points of view, reflecting existing practices and highlighting the need for consensus development. As the consensus panel approaches its deliberations, I would like to emphasize that the health of the child and family must be paramount. I define health in its broad sense as the physical, mental, and social well-being of children and families. Results of the collaborative oral penicillin study, presented by Dr Gaston, leave no doubt that identification of sickle cell disease during infancy and prevention of its complications are imperative. Also, many speakers from successful programs spoke of the extensive time, effort, and resources required to screen, follow up, counsel, and treat patients and to coordinate services. I request that the panel carefully consider the advisability and feasibility of a public health education program, patterned after the highly successful high blood pressure education program launched by the National Heart, Lung, and Blood Institute, which included every resource of the country.

scholarly journals Episodes of High Emergency Department Utilization Among a Cohort of Persons Living with Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 159-159
Author(s):  
Susan T Paulukonis ◽  
Eric Roberts ◽  
Ron Brathwaite ◽  
Ted Wun ◽  
Mary M Hulihan
Keyword(s):  
Health Care ◽  
Emergency Department ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Case Definition ◽  
Inpatient Stay ◽  
Cell Disease ◽  
One Year

Abstract Introduction: Previous research has shown that persons living with sickle cell disease (SCD) are at risk for frequent emergency department (ED) encounters, either with or without an associated inpatient stay. The disease manifests as acute onset vaso-occlusive crises or other severe and unpredictable complications that require immediate care. However, day hospital or other appropriate care settings to manage these health care events are not available to most of the population with SCD. Previous observations suggest that-while ED usage is high overall for this population-this usage is also episodic, with periods of high use interspersed with relatively low usage. We here seek to characterize both high-use and quiescent periods among patients seen in California non-federal hospitals over a 12-year period. Methods: The California Sickle Cell Data Collection project is a statewide effort to use a wide range of administrative, clinical, and other data sources to describe the population living with SCD, their health outcomes, and health care utilization patterns. The data here include 2005-2016 inpatient encounters and ED encounters (with or without an associated inpatient stay) linked by patient identifiers across data set and year. A validated case definition that suggests a high probability of a true SCD 'case' was applied: three or more occurrences of a SCD specific International Classification of Disease Code (version 9 or 10, depending on the year) within any 5 year period between 2005-2016. Only patients who met this case definition and had one year or more of follow-up time in the cohort were included in these analyses. We tabulated the numbers of encounters (inpatient and ED) for each patient for non-overlapping 4-week periods and used Poisson mixture models to evaluate whether encounter frequency could be characterized as a mixture of one or more discrete distributions. Based on these findings, we examined the timing and duration of periods of ED utilization for patients over the course of the study. Quiescent periods are defined as lengths of time in which a person has zero or near zero encounters in ED or inpatient settings. Occasional and high use periods of ED utilization are defined quantitatively by the model (as below). Results: There were 5,090 patients meeting the case definition with one year or more of time in follow up. Patients were followed for a median of 9.8 years (range 1.0 to 11.0). There were 94,196 ED encounters without and 59,064 ED encounters with an associated inpatient stay. A 3-component model best combined predictive power, parsimony, and clinical relevance (Figure 1, upper left), including quiescent periods (mean 0.09 encounters; 88.8% of 4-week periods); occasional-use periods (mean 1.28encounters; 10.8% of 4-week periods); and high-use periods (mean 7.48 encounters; 0.5% of 4-week periods). All but two of the subjects experienced at least one quiescent period during the study, 75.9% experienced at least one occasional-use period, and 8.0% experienced at least one high-use period. Spells of occasional- or high-use lasted a median of 8 weeks regardless of patient age, and 3.6% of these included at least some very high-use. Median lengths of quiescent periods were 24 weeks for patients aged less than 20 years, 16 weeks for those 20 years of age and older. Examples of distribution of utilization over time by certain patients are shown in Figure 1, upper right and both lower panels. Conclusions: The majority of patients with sickle cell disease experience discrete periods during which ED and inpatient hospital encounters are not uncommon, separated by somewhat longer periods with few-to-no encounters. The experiences of -8.0% of patients further include periods during which encounters were very frequent. Patients aged 20 years and older are more likely to experience these high frequency episodes. Further research is planned to identify whether particular health related events or patient characteristics are associated with these high-utilization spells. Figure 1 Figure 1. Disclosures Paulukonis: Bioverativ Inc.: Research Funding; Pfizer Inc.: Research Funding; Global Blood Therapeutics Inc.: Research Funding.

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