PedsQL™ Sickle Cell Disease Module: Feasibility, Reliability and Validity

Abstract Abstract 476 Background: Sickle cell disease (SCD) is an inherited chronic disease characterized by complications such as recurrent painful vaso-occlusive events that can require hospitalizations and contribute to early and increased mortality. Prior work using generic health-related quality of life (HRQL) instruments has demonstrated that patients with SCD experience significantly impaired HRQL in their baseline state of health that worsens during acute complications of the disease. To better understand differences in health status in children with SCD, we developed the PedsQL™ SCD Module to measure SCD-specific HRQL. The goal of this study was to determine the measurement properties for the child self- and parent-proxy reports for the newly developed PedsQL™ SCD Module. We hypothesized that the PedsQL™ SCD Module would be feasible and reliable and that children with more severe SCD would have worse HRQL than those with mild disease as measured by the PedsQL™ SCD Module. Methodology: This was a cross-sectional study conducted at 5 sites across the United States. Study participants were children with SCD ages 2–18 years who presented to clinic for a routine visit. HRQL was the main outcome measured with the newly developed 43-item PedsQL™ SCD Module which includes nine scales: Pain/Hurt (PH, 9 items), Pain Impact (PI, 10 items), Pain Management/Control (PMC, 2 items), Worry I (WO1, 5 items), Worry II (WO2, 2 items), Emotions (EM, 2 items), Treatment (TR, 7 items), Communication I (CO1, 3 items), Communication II (CO2, 3 items). Higher scores indicate better HRQL and lower SCD symptoms. Missing items were used to determine feasibility and Cronbach's alpha was used to determine reliability. HRQL of children with mild and severe disease were compared using an independent t-test to determine construct validity. Severe disease was defined as patients with 3 or more hospitalizations for pain in the 3 years prior, history of stroke and/or prior acute chest syndrome. Results: A total of 321 families (313 parents, 243 children ages 5–18 years) completed questionnaires. The average age of the children (46.7% boys) was 9.62 years (SD = 4.88). Feasibility was established, with 3% or less missing data for the module. The PedsQL™ SCD Module was reliable and distinguished between children with mild and severe SCD (Table 1). Conclusions: The PedsQL™ SCD Module performed well and demonstrated strong measurement properties in patients with SCD. Overall, both the parent-proxy report and child self-report differentiated between patients with severe and mild SCD supporting construct validity of the module. Although these are the first results using the PedsQL™ SCD Module, it has shown great potential as being a strong measure of HRQL for patients with SCD. Future studies incorporating the PedsQL™ SCD Module will benefit from the measure's disease-specific scales and overall ability to distinguish between mild and severe symptoms. Continually, these studies will help further define its' measurement properties and advance our knowledge of the HRQL in patients with SCD. Disclosures: Off Label Use: Hydroxyurea is approved for use in sickle cell disease in adults but not children. Varni:Mapi Research Trust: Dr. Varni holds the copyright and the trademark for the PedsQL™ and receives financial compensation from the Mapi Research Trust, which is a nonprofit research institute that charges distribution fees to for-profit companies that use the Pediatric Quality Other, PedsQL™, PedsQL™ Patents & Royalties.

Download Full-text

Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative Study of Sickle Cell Disease [see comments]

Blood ◽

10.1182/blood.v86.2.776.bloodjournal862776 ◽

1995 ◽

Vol 86 (2) ◽

pp. 776-783 ◽

Cited By ~ 321

Author(s):

FM Gill ◽

LA Sleeper ◽

SJ Weiner ◽

AK Brown ◽

R Bellevue ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Clinical Course ◽

The United States ◽

Beta Thalassemia ◽

Acute Chest Syndrome ◽

Cooperative Study ◽

Cell Disease ◽

Splenic Sequestration ◽

Clinical Events

Within the Cooperative Study of Sickle Cell Disease, 694 infants with confirmed sickle cell disease were enrolled at less than 6 months of age. Information about the nature and frequency of complications was collected prospectively over a 10-year period. Painful crises and acute chest syndrome were the most common sickle cell-related events in homozygous sickle cell anemia (SS), hemoglobin SC disease (SC), and S beta thalassemia patients (overall incidence in SS patients of 32.4 and 24.5 cases per 100 person-years, respectively). Bacteremia occurred most frequently in SS children under 4 years of age and in SC patients less than 2 years of age. The mortality rate was low in this cohort compared with that found in previous reports. Twenty children, all with Hb SS, died (1.1 deaths per 100 person-years among SS patients). Infection, most commonly with Streptococcus pneumoniae and Hemophilus influenzae, caused 11 deaths. Two children died of splenic sequestration, 1 of cerebrovascular accident, and 6 of unclear causes. Two patients underwent cholecystectomies, and 17 underwent splenectomies after one or more splenic sequestration crises. The experience of this cohort should reflect closely the true clinical course of those children with Hb SS and Hb SC disease who are observed in sickle cell centers in the United States.

Download Full-text

Abnormal Pulmonary Function in Adults with Sickle Cell Disease: Association of Decreased DLCO with Systemic Disease.

Blood ◽

10.1182/blood.v106.11.316.316 ◽

2005 ◽

Vol 106 (11) ◽

pp. 316-316 ◽

Cited By ~ 4

Author(s):

Elizabeth S. Klings ◽

Diego F. Wyszynski ◽

Vikki G. Nolan ◽

Martin H. Steinberg

Keyword(s):

Sickle Cell Disease ◽

Pulmonary Function ◽

Sickle Cell ◽

Pulmonary Function Tests ◽

Systemic Disease ◽

The United States ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Restrictive Physiology ◽

Abnormal Pulmonary Function

Abstract Pulmonary complications of sickle cell disease (SCD), including acute chest syndrome, pulmonary hypertension (PH) and pulmonary fibrosis, are common. Dyspnea and hypoxemia are equally common in this population. It is likely that pulmonary function tests (PFT) are abnormal in the SCD population, however, no extensive study has been reported to date. Moreover, the relationship between abnormal pulmonary function and other manifestations of SCD, such as PH, is unclear. We hypothesized that abnormalities of pulmonary function, particularly a low diffusion capacity for carbon monoxide (DLCO), may be associated with other complications of SCD. The Cooperative Study of Sickle Cell Disease (CSSCD) enrolled and followed more than 4,000 SCD patients who had visited one of 23 participating clinical centers across the United States between 1978 and 1998. Data were collected on many complications of the disease, and standardized collection of PFTs were part of the protocol. From the more than 1300 CSSCD patients who had the results of PFTs recorded, 310 adults (age≥ 20 years of age) homozygous for the Hb S gene without coincident α thalassemia and with sufficient data were identified. Predicted values for FEV1, FVC, FEV1/FVC, TLC, RV and DLCO were calculated using algorithms that accounted for gender, age, and height in the African American population (using STATA, version 9); data are presented as percent predicted. Based on criteria established by the American Thoracic Society, subjects were sub-classified into 7 groups: obstructive physiology; restrictive physiology; mixed obstructive/restrictive disease; low lung volumes with normal spirometry (LLV); LLV with a low DLCO, isolated low DLCO, or normal. The association of blood counts and serum chemistries between patients with low DLCO compared with those with a normal DLCO was assessed by multivariate linear regression (using SAS software version 8.2). Normal PFTs were present in only 31 of 310 (10 %) SCD patients. Overall, the adult SCD population was characterized by decreased total lung capacities (70.2 + 14.7% predicted) and DLCO (64.5 + 19.9 % predicted adjusted for hemoglobin concentration). The most common PFT patterns observed were restrictive physiology (35.8%), LLV with normal spirometry (34.2% of patients), and an isolated low DLCO (12.9%). The presence of a low DLCO was associated with an elevated platelet count (p=0.05), hepatic dysfunction [elevated ALT (p=0.07) with elevated AST (p=0.01)] and renal dysfunction [elevated BUN and creatinine (p=0.05, 0.07)]. Restrictive disease is marginally associated with a decrease in hematocrit (p=0.07) and Hb F levels (p=0.07). Pulmonary function is abnormal in 90% of adult SCD patients. Common abnormalities include restrictive physiology, LLV with normal spirometry and a decreased DLCO. The presence of a decreased DLCO may be a marker of more severe systemic disease that includes impaired renal and hepatic function and possibly complications of hemolytic anemia such as PH.

Download Full-text

Stem Cell Transplantation for Children with Sickle Cell Anemia: Factors Associated with Parent and Patient Interest

Blood ◽

10.1182/blood.v118.21.1079.1079 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1079-1079

Author(s):

Roth Michael ◽

Julie Krystal ◽

Deepa Manwani ◽

Catherine Driscoll ◽

Rosanna J. Ricafort

Keyword(s):

Stem Cell ◽

Sickle Cell Disease ◽

Life Span ◽

Disease Severity ◽

Sickle Cell ◽

The United States ◽

Life Goals ◽

Acute Chest Syndrome ◽

Cell Transplant ◽

Cell Disease

Abstract Abstract 1079 BACKGROUND: Sickle cell disease (SCD) is the most common inherited blood disorder in the United States affecting more than 70,000 children and adults. SCD is associated with significant morbidity and mortality with a mean life expectancy of approximately 45 years in patients with more severe Hb SS. Allogeneic hematopoietic stem cell transplant (HSCT) is the only curative treatment for sickle cell disease. Currently hematologists consider HSCT only for patients with a history of multiple pain crises, stroke, renal disease and/or multiple episodes of acute chest syndrome. However, factors that influence patients' and parents' interest in HSCT for SCD are not known. METHODS: We designed and administered a 40 question survey to assess the interest in HSCT as a cure for SCD in parents and adolescents with HbSS or HbSBetaThalassemia0. The survey tool assessed factors that may influence interest in HSCT including demographic data, disease severity, views on prognosis and Health Related Quality of Life (PedsQL4.0). All participants were given a handout on the risks and benefits of a HSCT prior to completing the survey. Participants' who responded they definitely or probably would undergo HSCT if recommended by their hematologist were categorized as “likely would undergo HSCT” while participants who responded they would maybe, probably not, or definitely would not undergo HSCT were categorized as “less likely would undergo HSCT”. RESULTS: Ninety parents and 42 adolescents completed the survey, with only 1 parent refusing to participate. Forty six percent (39/85) of parents would likely have their child undergo HSCT and 34% (14/41) of adolescents would likely undergo HSCT if it was recommended by their hematologist. Adolescents with better social function and better overall emotional function were more likely to undergo transplant (50% (10/20) vs. 19% (4/21), p=0.04) (53% (9/17) vs. 21% (5/24), p=0.03), respectively. Parents of children age>7 who believe their child's life span will be shortened secondary to SCD were more likely to undergo transplant (100% (3/3) vs. 35% (15/43), p=0.03). In addition, parents of children who have received an exchange transfusion were more likely to undergo transplant (62% (18/29) vs. 38% (20/53), p=0.04). Disease severity represented by the number of pain crises, episodes of acute chest, or presence of a stroke were not associated with increased parent or adolescent interest in HSCT. In addition, 50% (11/22) of parents of children who would not qualify for HSCT based on current disease severity criteria would likely undergo HSCT. In this cohort, parents who believed their child's disease would not get better were more likely to go forward with transplant (100% (5/5) vs. 31% (5/16), p=0.007). The majority of parents believe their child's sickle cell disease will get better (63% (55/87)), will not likely prevent their child from achieving life goals (83% (71/86)), and will not shorten their child's lifespan (88% (74/84)). Forty six percent (19/41) of adolescents believe their sickle cell disease will get better, 74% (31/42) believe it will not prevent them from achieving life goals, and 64% (27/42) believe sickle cell disease will not shorten their lifespan. CONCLUSIONS: There is a strong interest in HSCT in our patient cohort that was not pre-selected based on disease severity. Parents had an interest in HSCT based on both disease severity and perception of prognosis, while adolescents' interest in HSCT was directly related to higher psychosocial functioning. The current standard inclusion criteria for HSCT for children with SCD exclude a number of children whose parents are interested in HSCT. The finding of perception of a normal life span in the majority of patients and parents is troubling and suggests a need for more thorough education regarding the long term sequelae of SCD and the role for HSCT as a cure. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Hemoglobin F or: How I Learned to Stop Wondering and Love the Flow Cytometer

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz112.030 ◽

2019 ◽

Vol 152 (Supplement_1) ◽

pp. S15-S16

Author(s):

Roger Fecher ◽

Jui Choudhuri ◽

Mohammad Barouqa ◽

Seda Tolu ◽

Caterina Minniti ◽

...

Keyword(s):

Flow Cytometry ◽

Sickle Cell Disease ◽

Sickle Cell ◽

The United States ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Hemoglobin F ◽

Blood Disorder ◽

Cellular Concentration ◽

Hbf Level

Abstract Sickle cell disease (SCD) is the most common inherited blood disorder in the United States. It is a hemoglobinopathy that leads to red blood cell (RBC) sickling and a broad range of disease complications including vaso-occlusive crisis, acute chest syndrome, and retinopathy. Hydroxyurea, a drug used to treat SCD, is known to increase expression of hemoglobin F (HbF), a type of hemoglobin normally expressed in infancy; HbF levels between 10% and 20% are associated with decreased vaso-occlusive episodes and improved survival. Hereditary persistent hemoglobin F (HPHF), a typically asymptomatic hemoglobinopathy associated with sustained hemoglobin F (HbF) expression into adulthood (HbF >10%), in combination with SCD is associated with decreased complications. Laboratories typically determine the HbF level via high-performance liquid chromatography (HPLC). HbF levels approaching 30% on HPLC are thought to be protective against SCD complications. However, HbF may be found within a majority or minority of RBCs, pancellular (deletional HPHF) or heterocellular distribution (nondeletional HPHF), respectively. Additionally, the quantity of HbF within cells can range from low (<10 picograms/cell) to high (>35 picograms). We sought to determine the quantity and distribution of HbF required to protect against sickle cell disease symptoms both via traditional HPLC as well as flow cytometry. This retrospective study was conducted at a large academic medical center over a period of 2 months (January-February 2019). We collected blood from sickle cell patients that had a detectable HbF level on hemoglobin electrophoresis. We then stained RBCs from 16 of the patients for HbF and performed flow cytometry to examine the HbF distribution. We calculated the cellular concentration of HbF within each HbF+ cell using the formula (MHC × %HbF)/%F-cells. We performed a chart review to determine the native hemoglobin type, exposure to hydroxyurea, and clinical symptoms of sickle cell disease. We identified four patients over the age of 20 with HbS/HPHP and no exposure to hydroxyurea. Two of these patients experienced no sickle cell disease complications; the protected patients had heterocellular distribution of HbF, but had a high concentration of HbF per HbF+ cell (>35 picograms/cell). Notably, these asymptomatic patients both had HbF level by HPLC less than 30. One of the symptomatic HbS/HPHF patients had heterocellular expression of HbF with low cellular concentration (28 picograms/cell) while the other patient had pancellular HbF expression with very low cellular concentration (6.4 picograms/cell). Our study demonstrates that HPHF alone does not prevent sickle cell disease complications. Our study highlights the importance of quantifying the cellular concentration of HbF, which can provide useful information beyond that of HPLC. In addition, our study raises the potential of the clinical use of hydroxyurea in patients with sickle cell disease even in the presence of HPHF.

Download Full-text

Sickle Cell Disease Related Outcomes in Patients Evaluated for COVID-19 Infections in South Carolina

Blood ◽

10.1182/blood-2020-141359 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 38-39

Author(s):

Laurence Noisette ◽

Mamatha Mandava ◽

Mathew Gregoski ◽

Shayla Bergmann

Keyword(s):

South Carolina ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Clinical Presentation ◽

Self Report ◽

Mortality Data ◽

Acute Chest Syndrome ◽

Cell Disease ◽

History Of ◽

The Mean

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), first identified in Wuhan, China, was declared a pandemic by WHO in March 2020 due to its high transmission rate. Due to the diffuse vasculo-endothelial damage, individuals with Sickle Cell Disease (SCD) are at risk to develop severe clinical complications, if infected with coronavirus 19 (COVID-19).[1] Given this risk, a systematic evaluation of individuals with SCD presenting with COVID19 infection is paramount to identify the variable clinical manifestations and complications encountered in children and adults with SCD. Methods: A retrospective chart review was conducted from January to June 2020 at the Medical University of South Carolina. We included individuals with sickle cell disease of all genotypes, from 0 to 65 years of age found to be positive for COVID19 by polymerase chain reaction (PCR). Patients' past medical history, clinical presentations, admissions, treatment, complications, and mortality data were reviewed. The data was collected with REDCap@ and descriptive data analysis was conducted per SPSS@. Results: Of the identified 23 patients with SCD who tested positive for COVID during the time specified, 19 (82.6%) had Hgb SS genotype, two had Hgb SC (9%) and two Hgb Sβ+ thalassemia (9%) with similar incidence in both genders (47.8% male and 52.2 % female). All patients were African American. The mean age was 26.13+/-11.53 years. In the last three years they had admissions for pain at a mean of 4.29 +/- 5 and admissions for acute chest syndrome 1+/- 2.2. Six participants (26.1%) had history of mild asthma. Two (8.7%) had pulmonary hypertension. No participants had a history of silent stroke. One participant had history of ischemic stroke, three (13%) had history of pulmonary embolism, and six (26.1%) had deep vein thrombosis (DVT). A variable clinical presentation was noted in our population (Table 1). Of the 23, only nine (39%) required admission of which only one met criteria for intensive care (4.3%) requiring respiratory support with high flow nasal canula. All participants recovered well with the mean length of admission 4.36+/- 3.8 days. Treatment included supportive care including transfusion support, two (8.7%) needed simple transfusion, two (8.7%) needed exchange transfusion. Regarding the laboratory values, coagulations studies were noted to be elevated among all those obtained, but overall limited values were obtained. (Table 2) Thus far no complications of stroke, thrombosis, or pulmonary emboli are noted in the patients positive for COVID in sickle cell disease at our institution. No deaths were reported. Conclusion: Our population reflects what has been described thus far in other cohorts regarding patient demographics, clinical presentation and evolution of disease. Missing laboratory results is most likely due to the mild severity which did not require further clinical evaluation. The absence of VTE/PE may be explained by the low rate of ICU admissions. A similar ICU admission rate of 13% in the same age group as our population was described in a study conducted in France with 83 patients. [2] Compared to a study conducted in Detroit, Michigan, our population underwent comparable rates of transfusions with 3 patients compared to 4 in our population, again most likely due to the mild severity. [3] Our results reflect only MUSC's testing sites and we are dependent on patient's self-report which may not represent our entire population. To address this issue, as part of the Sickle Cell South Carolina network, we are partnering with two other institutions to assess SARS-Cov-2 infection in South Carolina. SARS-CoV-2 pandemic has brought to light many disparities encountered in the American health care system. It is premature to evaluate the immediate and long-term ramifications of COVID19 in individuals with sickle cell disease, due to which we plan to continue to monitor for the next 2 years. References 1. Hussain, F.A., et al.,COVID-19 Infection in Patients with Sickle Cell Disease.Br J Haematol, 2020. 2. Arlet, J.B., et al.,Prognosis of patients with sickle cell disease and COVID-19: a French experience.Lancet Haematol, 2020. 3. Balanchivadze, N., et al.,Impact of COVID-19 Infection on 24 Patients with Sickle Cell Disease. One Center Urban Experience, Detroit, MI, USA.Hemoglobin, 2020: p. 1-6. Disclosures Gregoski: National Institutes of Health under Grant Number UL1 TR001450:Current Employment.

Download Full-text

Sex-based differences in the manifestations and complications of sickle cell disease: Report from the Sickle Cell Disease Implementation Consortium

PLoS ONE ◽

10.1371/journal.pone.0258638 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0258638

Author(s):

Rita V. Masese ◽

Dominique Bulgin ◽

Mitchell R. Knisely ◽

Liliana Preiss ◽

Eleanor Stevenson ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Hospital Admissions ◽

Pain Treatment ◽

Multivariable Analysis ◽

Self Report ◽

Future Research ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Eligibility Criteria

Introduction Sex-based clinical outcome differences in sickle cell disease (SCD) remain largely unknown despite evidence that female sex is associated with an increased lifespan. To better characterize sex-based differences in SCD, we assessed pain, treatment characteristics, laboratory measures and complications among males and females currently enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. Methods The SCDIC consists of eight comprehensive SCD centers and one data coordinating center that received funding from the National Heart Lung and Blood Institute to improve outcomes for individuals with SCD. Eligibility criteria included: 15 to 45 years of age and a confirmed diagnosis of SCD. Self-report surveys were completed and data were also abstracted from the participants’ medical records. Results A total of 2,124 participants were included (mean age: 27.8 years; 56% female). The majority had hemoglobin SS SCD genotype. Females had worse reports of pain severity (mean (SD) T-score 51.6 (9.6) vs 49.3 (10), p<0.001), more vaso-occlusive episodes (p = 0.01) and a higher occurrence of 3 or more hospital admissions in the past year (30.9% vs. 25.5, p = 0.03). On multivariable analysis, males had higher odds of acute chest syndrome (odds ratio (OR) 1.4, p = 0.002), cardiovascular (OR 1.70, p<0.001) and musculoskeletal (OR 1.33, p = 0.0034) complications and lower odds of depression (OR 0.77, p = 0.0381). Females had higher fetal hemoglobin levels with and without hydroxyurea use (9.6% vs 8.5%, p = 0.03 and 3% vs 2.2%, p = 0.0005, respectively). Conclusion Our data suggests that sex differences in clinical outcomes do occur among individuals with SCD. Future research needs to explore the mechanisms underlying these differences.

Download Full-text

Acute compartment syndrome in a patient with sickle cell disease

Annals of The Royal College of Surgeons of England ◽

10.1308/rcsann.2020.0160 ◽

2020 ◽

Vol 102 (9) ◽

pp. e1-e2

Author(s):

E Cochrane ◽

S Young ◽

Z Shariff

Keyword(s):

Sickle Cell Disease ◽

Compartment Syndrome ◽

Sickle Cell ◽

Rare Complication ◽

The United States ◽

Acute Compartment Syndrome ◽

Acute Chest Syndrome ◽

Cell Disease ◽

The United Kingdom ◽

Considerable Morbidity

Haemoglobin SC (HbSC) disease accounts for 30% of cases of sickle cell disease in the United Kingdom and the United States. Unlike other sickle cell carriers, who are relatively asymptomatic, people with HbSC disease have a combination of genotypes with the potential to cause considerable morbidity due to intracellular water loss. Patients can present with acute pain, acute chest syndrome, proliferative retinopathy, splenic and renal complications, or stroke. We present a young man with HbSC disease who developed acute compartment syndrome. This is only the second report of this syndrome in a patient with HbSC disease. This is a very rare complication in HbSC disease, but it can have serious implications.

Download Full-text

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

Blood ◽

10.1182/blood-2021-144636 ◽

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.

Download Full-text

Sickle Cell Disease

10.2310/em.4037 ◽

2015 ◽

Author(s):

Caroline Freiermuth ◽

Idan Cudykier

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Blood Cells ◽

Genetic Basis ◽

Globin Gene ◽

The United States ◽

Acute Chest Syndrome ◽

Cell Disease ◽

The Past ◽

Pain Medications

Sickle cell disease affects between 70,000 and 90,000 individuals in the United States, the majority of whom are of African-American descent. The genetic basis of the disease is an abnormality in the β-globin gene, which causes the red blood cells to change to a “sickle” shape due to low oxygenation. The life span of patients with this disease has improved over the past few decades, although morbidity remains high. This review covers the pathophysiology of sickle cell disease and the stabilization and assessment, diagnosis and treatment, maintenance and preventive therapies, and cure of patients with sickle cell disease. Figures show hemoglobin electrophoresis; age at death for individuals with sickle cell disease in the years 1979, 1989, 1999, and 2006; sickled cells blocking blood flow; acute chest syndrome; dactylitis; and avascular necrosis. Tables list important trials, topics in need of further research, common complications, most common intravenous pain medications, and indications for transfusion. This review contains 6 highly rendered figures, 5 tables, 97 references, and a list of educational resources.

Download Full-text

Identification of the Pitfalls in the Attempted Use of Extracorporeal Membrane Oxygenation in an Adult Patient with Sickle Cell Disease and Severe Acute Chest Syndrome

Blood ◽

10.1182/blood-2019-131561 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4854-4854

Author(s):

Mira T Tanenbaum ◽

Anna Shvygina ◽

Vaishnavi Sridhar ◽

Jennifer E. Vaughn ◽

Mark Joseph

Keyword(s):

Case Report ◽

Sickle Cell Disease ◽

Extracorporeal Membrane Oxygenation ◽

Adult Patient ◽

Sickle Cell ◽

Case Reports ◽

The United States ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Membrane Oxygenation

BACKGROUND: Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Despite being the leading cause of death in adult patients with SCD, current recommendations for treatment of ACS remain largely supportive, consisting of pain management, aggressive fluid resuscitation, respiratory support, and transfusion therapy. Despite these measures, it is not uncommon for patients to require intubation due to progression to acute respiratory distress syndrome (ARDS). Recently, there have been a number of case reports that have successfully utilized extracorporeal membrane oxygenation (ECMO) for the management of ACS in those patients who fail to respond to conventional therapy [Kuo et al., 2013, Sewaralthahab et al, 2018]. However, the use of ECMO in this patient population remains uncommon, and further evaluation of this intervention is needed. This case report details an unsuccessful attempt at the use of ECMO in the case of ARDS secondary to ACS, in an attempt to identify critical pitfalls. CASE REPORT: A 32-year-old African-American female with HbSS disease on hydroxyurea therapy was transferred from an outside hospital following 3 days of respiratory decompensation. Prior to arrival, patient coded once at the outside hospital and once on transfer. Veno-arterial ECMO was initiated with improving oxygen saturation and volume status with continuous renal replacement therapy. To maintain an ECMO-specific goal hemoglobin level of 10 g/dL, 1:1 manual exchange transfusions were performed due to an inability to access equipment for automated RBC exchange. Once stable enough for CT, patient was found to have gray-white inversion suggestive of irreversible severe brain damage. Following another 28 days of supportive care with no neurologic improvement, the family decided to withdraw care, and the patient expired. CONCLUSION: While unsuccessful, this patient's case revealed a need for defining parameters regarding the initiation of ECMO in SCD patients with severe ACS. A review of previously-published literature has shown that the use of ECMO for the management of ARDS in adults is more efficacious than conventional ventilation support [Peek et al., 2009]. In patients with SCD, this improvement in efficacy is not readily reproduced, likely due to unique challenges presented by the pathophysiology of the disease. Notably, patients with SCD face additional risks of venous thromboembolism and strokes while on prolonged bed rest due to a baseline prothrombotic state [Sewaralthahab et al., 2018]. A systematic review of available case reports is needed to develop a protocol for the management of severe ACS that takes SCD-specific risks into account. The present report also makes a case for the training of providers in the early recognition of severe ACS in SCD patients. SCD remains largely undertreated in the United States, likely due to a complex interplay of patient, physician, and institutional factors. Had this patient been transferred immediately to a facility better equipped to provide a higher level of care, her condition could have arguably taken a different course. Despite the aforementioned challenges, ECMO remains a feasible option for the management of severe ACS in patients with SCD, and efforts should be made to standardize current treatment protocols. REFERENCES: Kuo KW, Cornell TT, Shanley TP, Odetola FO, and Annich GM. The use of extracorporeal membrane oxygenation in pediatric patients with sickle cell disease. Perfusion. 2013 September; 28(5): 424-432. Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany M, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. The Lancet. 2009 October; 374(9698): 1351-1363. Sewaralthahab SS, Menaker J, Law JY. Successful use of veno-venous extracorporeal membrane oxygenation in an adult patient with sickle cell anemia and severe acute chest syndrome. Hemoglobin. 2018 42(1): 65-67. Disclosures No relevant conflicts of interest to declare.

Download Full-text