Burden of Sickle Cell Disease: A Brazilian Societal Perspective Analysis

Introduction: Sickle cell disease (SCD) is a group of inherited disorders that shorten life expectancy. It is estimated that 300,000 children are born with the disease worldwide each year [1,2]. In Brazil is it estimated that 3,500 children are born with SCD each year [3]. The SCD is a multisystem disorder that leads to several complications (acute and chronic) including vaso-occlusive crisis [1,4]. SCD patients experience increase morbidity and mortality, the implications of which are known to impacts the whole society [2]. Although there is some knowledge about the clinical impacts of SCD, little is known about the societal costs. Due to the limited available, to the best of our knowledge there are no similar studies which have been conducted and published. The aim of this study is to estimate SCD societal costs based on a burden of disease model, utilizing the Brazilian societal perspective. Material and Methods: A burden of disease model (Figure 1) was built considering direct medical costs to adults and children and indirect costs, taking into account lost wages due to SCD related morbidity and death. Direct costs were estimated using a bottom-up strategy and micro-costing method, and indirect costs were estimated using a prevalence method. Disability-adjusted life years (DALYs) were calculated from the sum of years of life lost and disability. The rate and duration of SCD related complications (including death) was calculated using information from a Brazilian governmental healthcare public database (DATASUS). The prevalence of each complication was determined by literature data or medical experts. It is important to point that there is some uncertainty around the prevalence estimates. Direct costs for complications were captured from the Brazilian public healthcare system table of procedures and medications (SIGTAP). Indirect costs attributed to productivity loss were calculated using the human capital method. All values were reported in 2020 Brazilian real (BRL). Results: Considering a prevalence of 23.9 cases per 100,000 (50,000 patients in 2018) and a probability of death of 1.11% (560 deaths in 2018), the annual total SCD cost in Brazil was estimated at 1,519,473,501 BRL. Table 1 shows the contribution of the direct and indirect costs to the total cost for the SCD population in Brazil. Further, results were stratified by children and adults (56% and 44%, respectively). Indirect cost was the main driver of disease burden, estimated at 1,128,355,824 BRL. Approximately 40,829 DALYs were lost by SCD patients in 2018 (22,750 and 18,079 among adults and children, respectively). Direct medical costs represented 25.7% of total costs and were estimated at 391,117,677 BRL. Provision of standard of care was the main driver of direct costs in both populations (157,521,597 BRL for adults and 100,133,575 BRL for children). Chronic complication management was shown to be more expensive than acute complication management among adults, while the opposite was observed for children. Vaso-occlusive crisis was the acute complication most frequently observed in available literature and according to medical experts (75.0% among adults and 59.5% among children). Acute chest syndrome had the highest disability weight (0.33). Considering chronic complications, calculous chronic cholecystitis was considered the most frequent among adults (62.0%) and renal abnormalities (without failure) among children (20.0%). Conclusion: SCD patients generate a high economic burden for the Brazilian society greater than one point five billion BRL per year. Most of the cost is related to indirect burden due to increased mortality and morbidity. Investments in technologies and therapies that can decrease the impact of SCD on patients' lives by reducing morbidity and/or mortality are necessary. References: 1. Kato GJ, Piel FB, Reid CD, Gaston MH, Ohene-Frempong K, Krishnamurti L, et al. Sickle cell disease. Nat Rev. 2018 Jun 15;4(1):18010. 2. Mburu J, Odame I. Sickle cell disease : Reducing the global disease burden. 2019;41(February):82-8. 3. Carneiro-Proietti ABF, Kelly S, Miranda Teixeira C, Sabino EC, Alencar CS, Capuani L, et al. Clinical and genetic ancestry profile of a large multi-centre sickle cell disease cohort in Brazil. Br J Haematol. 2018 Sep;182(6):895-908. 4. Piel FB, Steinberg MH, Rees DC. Sickle Cell Disease. Longo DL, editor. N Engl J Med. 2017 Apr 20;376(16):1561-73. Figure 1 Disclosures Pinto: Novartis: Consultancy. Costa:Novartis: Consultancy. Gualandro:Novartis: Consultancy. Fonseca:Novartis: Consultancy. Bueno:Novartis: Current Employment. Cançado:Novartis: Consultancy.

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Effects of Genotypes and Treatment on Oxygenscan Parameters in Sickle Cell Disease

Cells ◽

10.3390/cells10040811 ◽

2021 ◽

Vol 10 (4) ◽

pp. 811

Author(s):

Camille Boisson ◽

Minke A. E. Rab ◽

Elie Nader ◽

Céline Renoux ◽

Celeste Kanne ◽

...

Keyword(s):

Steady State ◽

Sickle Cell Disease ◽

Blood Cell ◽

Sickle Cell ◽

Red Blood Cell ◽

Cell Disease ◽

Oxygen Gradient ◽

Acute Complication ◽

Adults And Children ◽

The Difference

(1) Background: The aim of the present study was to compare oxygen gradient ektacytometry parameters between sickle cell patients of different genotypes (SS, SC, and S/β+) or under different treatments (hydroxyurea or chronic red blood cell exchange). (2) Methods: Oxygen gradient ektacytometry was performed in 167 adults and children at steady state. In addition, five SS patients had oxygenscan measurements at steady state and during an acute complication requiring hospitalization. (3) Results: Red blood cell (RBC) deformability upon deoxygenation (EImin) and in normoxia (EImax) was increased, and the susceptibility of RBC to sickle upon deoxygenation was decreased in SC patients when compared to untreated SS patients older than 5 years old. SS patients under chronic red blood cell exchange had higher EImin and EImax and lower susceptibility of RBC to sickle upon deoxygenation compared to untreated SS patients, SS patients younger than 5 years old, and hydroxyurea-treated SS and SC patients. The susceptibility of RBC to sickle upon deoxygenation was increased in the five SS patients during acute complication compared to steady state, although the difference between steady state and acute complication was variable from one patient to another. (4) Conclusions: The present study demonstrates that oxygen gradient ektacytometry parameters are affected by sickle cell disease (SCD) genotype and treatment.

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Indirect costs of sickle cell disease high in USA

PharmacoEconomics & Outcomes News ◽

10.1007/s40274-021-07955-x ◽

2021 ◽

Vol 885 (1) ◽

pp. 13-13

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Indirect Costs ◽

Cell Disease

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Pulmonary Hypertension in Sickle Cell Disease: A Common Complication for Both Adults and Children.

Blood ◽

10.1182/blood.v104.11.1666.1666 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1666-1666 ◽

Cited By ~ 1

Author(s):

Claudia R. Morris ◽

Jennifer Gardner ◽

Ward Hagar ◽

Elliott P. Vichinsky

Keyword(s):

Pulmonary Hypertension ◽

Liver Disease ◽

Sickle Cell Disease ◽

Renal Disease ◽

Sickle Cell ◽

Significant Risk ◽

Common Complication ◽

Cell Disease ◽

History Of ◽

Adults And Children

Abstract Pulmonary hypertension (PHT) is a risk factor for death in adults with sickle cell disease (SCD). Although occurring in >30% of adult patients, routine screening is not yet standard of care, and many patients are undiagnosed and untreated. Little is known on the prevalence of PHT in the pediatric population. A retrospective chart review was performed on 362 patients to evaluate screening practices and prevalence of PHT in both adults and children with SCD. Thirty percent (n=110) were < 18 years old, and gender was equally distributed. This review identified 96 patients with PHT (TRjet ≥2.5 m/sec by echo), suggesting a prevalence of 26.5%. However, since only 57% were screened by echo, this prevalence is grossly underestimated. Many echos documenting a TRjet ≥2.5 m/sec were interpreted by a cardiologist as NOT having PHT, likely because abnormal PAP in SCD are lower than in primary PHT. Of patients screened by echo, 46% had PHT (75 SS, 13 SC, 8 Sb-thal). Only 51% were identified by a clinician as having PHT, and only 4% were receiving treatment (chronic transfusion). Fifteen children had PHT. While 11 carried the diagnosis, none were on therapy. There was no difference in the percentage of adults vs. children screened by echo, however 56% of adults screened had PHT compared to 25% of children screened. Patients screened by echo were more likely to be male, homozygous for SS and were generally a sicker population. Patients found to have PHT were older (r=0.22, p<0.0001), and had a higher incidence of asthma, VOC episodes, gallbladder and renal disease, hepatitis C, smoking, alcohol and/or drug abuse, >LFTs, >creatinine, and more were on oxygen and/or hydroxyurea therapy compared to those without PHT. Surprisingly, history of ACS and splenectomy was similar in both groups. Comparing adults to children with PHT, more men than women were affected among adults (however more men were screened), while gender was equally distributed among children. Age of children with PHT ranged from 7–17 years (mean 12.6±3 years). Children were more likely to be homozygous for SS (14/15), carry the diagnosis of PHT, have a history of ACS (93% vs. 52%), and a higher incidence of sepsis (40% vs. 14%) than their adult counterparts. However they had fewer complications overall; renal and liver disease was rare, and less were transfused. Compared to children who do not have PHT, kids with PHT are more likely to have a history of ACS (93% vs. 63%), an abnormal CXR (87% vs. 57%), asthma (33% vs. 15%), >VOC events (60% vs. 39%), history of sepsis (40% vs. 9%), but less stroke (7% vs. 17%) and less transfusions including chronic transfusion (27% vs. 50%). It is possible that early transfusion secondary to a CNS event is protective against the development of PHT in children. Stepwise logistical regression modeling included renal disease, chronic transfusion, liver disease and alcohol use as significant risk factors for PHT (ROC = 0.82). Current mortality rate is 2% for patients without PHT vs. 8% for the PHT group (p=0.03). In conclusion, PHT is a common complication in SCD that affects both adults and children. The diagnosis is often missed, even with echo evidence of PHT. In this population 96% were untreated. Children with PHT have a different profile of complications than adults with PHT, suggesting alternate mechanisms of disease pathogenesis in children. Since PHT is associated with high mortality and morbidity, universal screening by echo and increased awareness is essential to identify patients at risk, and new therapies are critically needed.

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Disease Burden and Pre-Transplant Health-Related Quality of Life in Pediatric Sickle Cell Disease Patients Receiving Nonmyeloablative HLA-Identical Sibling Donor Transplantation

Blood ◽

10.1182/blood-2021-153310 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4073-4073

Author(s):

Jeremy Zack ◽

Robert Sheppard Nickel ◽

Allistair Abraham ◽

Steven J. Hardy

Keyword(s):

Quality Of Life ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Disease Burden ◽

Health Related Quality ◽

Cell Disease ◽

Related Quality ◽

Health Related ◽

History Of

Abstract Title: Disease Burden and Pre-transplant Health-related Quality of Life in Pediatric Sickle Cell Disease Patients Receiving Nonmyeloablative HLA-identical Sibling Donor Transplantation Background: Sickle cell disease (SCD) is a hemoglobinopathy characterized by recurrent pain crises, severe organ damage, and reduced health-related quality of life (HRQL). Bone marrow transplantation (BMT) is a proven curative treatment for SCD that can improve both disease burden and HRQL. Despite the benefits, relatively few patients pursue a cure through BMT. The decision to receive a BMT is nuanced and likely to be influenced by a number of factors. One study by Roth et al. showed SCD patients interested in BMT had a higher HRQL than those uninterested in BMT, suggesting some variability between SCD patients pursuing transplant and the general SCD patient population. To date the factors that may affect pre-transplant HRQL of pediatric SCD patients remain unclear, particularly in the nonmyeloablative setting. Objective: To evaluate the impact of disease-burden, patient demographics, and hydroxyurea treatment on pre-transplant HRQL. Methods: Children and young adults with SCD set to receive a nonmyeloablative HLA-identical sibling donor BMT were administered HRQL surveys (PedsQL) in the six months leading up to the start of the conditioning regimen. Patients' disease history and demographic information were captured and analyzed for their relationship to HRQL. PedsQL parent surveys were used when patient surveys were unavailable. The mean difference in HRQL between groups were compared using an unpaired t test or linear regression. Results: 32 patients were enrolled onto this study. Six of the 32 patients HRQL were not included due to withdrawal, delay of transplant, or completion of the survey outside of window. The median age at the time of survey administration was 13.5 years (range 2-21). 57.7% of patients were male and 88% of patients had genotypes hemoglobin SS or Sβ 0thalassemia. 12% of patients had a history of overt stroke. 52% of patients were hospitalized while receiving HU treatment. 32% of patients received chronic blood transfusions leading up to transplant. The median number of hospitalizations in the two years leading up to transplant was 2 (range 0-10). 16.7% of patients met the AAPT diagnostic criteria for chronic pain. 75% of patients received HU treatment leading up to transplant. The median hemoglobin F percentage was 10.4. The median HRQL for all patients was 77.17 (range 36.9-98.91, SD +/- 15.99). Sickle cell genotype (P=0.88), history of overt stroke (P=0.79), hospitalization while receiving HU treatment (P=0.78), and the number of hospitalizations in the two years before transplant (P=0.39) were not associated with lower HRQL. History of chronic transfusion leading up to transplant approached statistical significance for lower HRQL (P=0.06). Older age (P=0.17) and female gender (P=0.89) were not associated with worse HRQL. Patients receiving HU treatment had significantly higher HRQL than patients not receiving HU (P=0.0034), with median PedsQL scores of 80.06 and 58.64, respectively. The date of survey administration was not associated with HRQL (P=0.40). The number of eligibility criteria met (P=0.63), chronic pain (P=0.17), total number of RBC transfusions (P=0.45), and pre-transplant hemoglobin (P=0.25) were not associated with HRQL. Discussion: Patient demographics and several markers of disease burden appear to have minimal impact on HRQL. Interestingly, the use of HU therapy was associated with significantly higher pre-transplant HRQL. The etiology of this finding is unclear given that disease burden was not associated with HRQL and warrants further investigation. The absence of association between disease burden and HRQL through current disease severity eligibility paradigms suggests that other factors may impact HRQL in SCD patients choosing a low toxicity nonmyeloablative BMT. Disclosures No relevant conflicts of interest to declare.

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Pulmonary disease burden in Hispanic and non‐Hispanic children with sickle cell disease

Pediatric Pulmonology ◽

10.1002/ppul.24883 ◽

2020 ◽

Vol 55 (8) ◽

pp. 2064-2073

Author(s):

Laura Chen ◽

Jacqueline Gong ◽

Esther Matta ◽

Kerry Morrone ◽

Deepa Manwani ◽

...

Keyword(s):

Sickle Cell Disease ◽

Pulmonary Disease ◽

Sickle Cell ◽

Disease Burden ◽

Cell Disease ◽

Hispanic Children

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Higher Pulmonary Disease Burden among Hispanic Children with Sickle Cell Disease

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a4387 ◽

2019 ◽

Author(s):

L. Chen ◽

J. Gong ◽

E. Matta ◽

K. Morrone ◽

D. Manwani ◽

...

Keyword(s):

Sickle Cell Disease ◽

Pulmonary Disease ◽

Sickle Cell ◽

Disease Burden ◽

Cell Disease ◽

Hispanic Children

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Allogeneic hematopoietic stem cell transplantation for sickle cell disease: the time is now

Blood ◽

10.1182/blood-2011-01-332510 ◽

2011 ◽

Vol 118 (5) ◽

pp. 1197-1207 ◽

Cited By ~ 81

Author(s):

Matthew M. Hsieh ◽

Courtney D. Fitzhugh ◽

John F. Tisdale

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Disease Burden ◽

Conditioning Regimen ◽

Adult Patients ◽

Cell Disease ◽

Hematopoietic Stem ◽

Alternative Donor ◽

Hematopoietic Chimerism ◽

Matched Sibling

Abstract Although sickle cell disease (SCD) has a variable clinical course, many patients develop end-organ complications that are associated with significant morbidity and early mortality. Myeloablative allogeneic HSCT (allo-HSCT) is curative but has been historically performed only in children younger than 16 years of age. Modest modifications in the conditioning regimen and supportive care have improved outcome such that the majority of children with a suitable HLA-matched sibling donor can expect a cure from this approach. However, adult patients have been excluded from myeloablative allo-HSCT because of anticipated excess toxicity resulting from accumulated disease burden. Efforts to use nonmyeloablative transplantation strategies in adults logically followed but were initially met with largely disappointing results. Recent results, however, indicate that nonmyeloablative allo-HSCT in adult patients with SCD allows for stable mixed hematopoietic chimerism with associated full-donor erythroid engraftment and normalization of blood counts, and persistence in some without continued immunosuppression suggests immunologic tolerance. The attainment of tolerance should allow extension of these potentially curative approaches to alternative donor sources. Efforts to build on these experiences should increase the use of allo-HSCT in patients with SCD while minimizing morbidity and mortality.

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