Sickle Cell Disease

Piel, Frédéric B.; Steinberg, Martin H.; Rees, David C.

doi:10.1056/nejmc1706325

Cited by 306 publications

(13 citation statements)

References 52 publications

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“…Sickle cell disease (SCD) is a group of inherited red blood cell disorders in which abnormality in haemoglobin beta gene results in abnormal shape and sickling of red blood cells under stress. Physiological manifestations of the illness arise from end organ ischaemia, including acute pain from vaso-occlusive crises, cerebrovascular accident, acute chest syndrome, pulmonary hypertension, heart failure, renal failure, severe anaemia, and recurrent infections 1. Approximately 100 000 Americans predominantly of African (90%), Middle Eastern and Mediterranean descent are affected by SCD 2.…”

Section: Introductionmentioning

confidence: 99%

Inpatient palliative care use by patients with sickle cell disease: a retrospective cross-sectional study

et al. 2022

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ObjectiveSickle cell disease (SCD) is a highly morbid condition notable for recurrent hospitalisations due to vaso-occlusive crises and complications of end organ damage. Little is known about the use of inpatient palliative care services in adult patients with SCD. This study aims to evaluate inpatient palliative care use during SCD-related hospitalisations overall and during terminal hospitalisations. We hypothesise that use of palliative care is low in SCD hospitalisations.DesignA retrospective cross-sectional study using data from the National Inpatient Sample from 2008 to 2017 was conducted.SettingUS hospitals from 47 states and the District of Columbia.ParticipantsPatients >18 years old hospitalised with a primary or secondary International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or ICD-10-CM diagnosis of SCD were included.Primary and secondary outcome measuresPalliative care service use (documented by ICD-9-CM and ICD-10-CM diagnosis codes V66.7 and Z51.5).Results987 555 SCD-related hospitalisations were identified, of which 4442 (0.45%) received palliative care service. Palliative care service use increased at a rate of 9.2% per year (95% CI 5.6 to 12.9). NH-black and Hispanic patients were 33% and 53% less likely to have palliative care services compared with NH-white patients (OR 0.67; 95% CI 0.45 to 0.99 and OR 0.47; 95% CI 0.26 to 0.84). Female patients (OR 0.40; 95% CI 0.21 to 0.76), Medicaid use (OR 0.40; 95% CI 0.21 to 0.78), rural (OR 0.47; 95% CI 0.28 to 0.79) and urban non-teaching hospitals (OR 0.61; 95% CI 0.47 to 0.80) each had a lower likelihood of palliative care services use.ConclusionUse of palliative care during SCD-related hospitalisations is increasing but remains low. Disparities associated with race and gender exist for use of palliative care services during SCD-related hospitalisation. Further studies are needed to guide evidence-based palliative care interventions for more comprehensive and equitable care of adult patients with SCD.

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Section: Introductionmentioning

confidence: 99%

Inpatient palliative care use by patients with sickle cell disease: a retrospective cross-sectional study

et al. 2022

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“…Sickle cell disease (SCD) is a monogenic autosomal recessive disorder defined by a missense mutation in the b-globin gene, forming the sickle hemoglobin (HbS) (1). Affecting nearly 300'000 newborns per year with the highest prevalence in sub-Saharan Africa, India, and the Mediterranean and Middle East regions, SCD imposes a considerable global health burden (2,3). The substitution of glutamic acid with the hydrophobic amino acid valine at position 6 in the b-globin gene causes erythrocyte hemoglobin to polymerize and facilitate red blood cells (RBCs) sickling under deoxygenation (4).…”

Section: Introductionmentioning

confidence: 99%

Agonistic Anti-CD40 Antibody Triggers an Acute Liver Crisis With Systemic Inflammation in Humanized Sickle Cell Disease Mice

et al. 2021

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Sickle cell disease (SCD) is an inherited hemolytic disorder, defined by a point mutation in the β-globin gene. Stress conditions such as infection, inflammation, dehydration, and hypoxia trigger erythrocyte sickling. Sickled red blood cells (RBCs) hemolyze more rapidly, show impaired deformability, and increased adhesive properties to the endothelium. In a proinflammatory, pro-coagulative environment with preexisting endothelial dysfunction, sickled RBCs promote vascular occlusion. Hepatobiliary involvement related to the sickling process, such as an acute sickle hepatic crisis, is observed in about 10% of acute sickle cell crisis incidents. In mice, ligation of CD40 with an agonistic antibody leads to a macrophage activation in the liver, triggering a sequence of systemic inflammation, endothelial cell activation, thrombosis, and focal ischemia. We found that anti-CD40 antibody injection in sickle cell mice induces a systemic inflammatory and hemodynamic response with accelerated hemolysis, extensive vaso-occlusion, and large ischemic infarctions in the liver mimicking an acute hepatic crisis. Administration of the tumor necrosis factor-α (TNF-α) blocker, etanercept, and the heme scavenger protein, hemopexin attenuated end-organ damage. These data collectively suggest that anti-CD40 administration offers a novel acute liver crisis model in humanized sickle mice, allowing for evaluation of therapeutic proof-of-concept.

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“…SCD is the most common monogenic disorder with high prevalence among individuals originating from Sub-Saharan Africa, Middle East, South Asia, and the Mediterranean. 2 In the United States, about 1.5% of newborns screen positive for a beta hemoglobinopathy, and over 100,000 people have SCD 3 . Among African Americans, about 1 in 12 are carriers and 1 in 365 are affected with SCD.…”

Section: Introductionmentioning

confidence: 99%

Clinical validity of single-gene non-invasive prenatal testing for sickle cell disease and beta thalassemia

Westin

Tsao

Atay

et al. 2021

Preprint

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Background: Sickle cell disease (SCD) and beta thalassemia (β-thalassemia) are among the most common and severe genetically inherited disorders in the world. Although the maternal carrier status of these beta hemoglobinopathies is screened as a part of routine prenatal care in the US, the paternal carrier status is usually unavailable. Under this current screening paradigm, identification of the majority of SCD and beta thalassemia cases could therefore be delayed until newborn screening results are available. An effective reflex, non-invasive prenatal test (NIPT) that uses only maternal blood would permit prenatal detection of sickle cell disease and beta thalassemia by screening for these disorders without the need for paternal DNA. This screening would enable patients and healthcare providers to make informed decisions about diagnostic testing, and it could expand gene therapy treatment options by requesting cord blood banking at delivery. We have previously developed a single-gene NIPT platform (UNITY™) for SCD and beta thalassemia with extensive analytic validation and initial clinical validation in our prior studies. Objectives: The objective of this study is to further assess the clinical validity of single-gene NIPT for SCD and beta thalassemia in a larger pregnancy population. Study Design: Pregnant women who screened positive for at least one allele of a beta hemoglobinopathy were enrolled at two academic medical centers for this retrospective cohort study. Single-gene NIPT for SCD and beta thalassemia was performed in blinded fashion on maternal blood samples to determine the fetal genotype and disease status. Single-gene NIPT findings were compared with either newborn screen results or genotyping of umbilical cord blood. Results: Single-gene NIPT detection of fetuses that are affected versus unaffected with SCD and beta thalassemia was 100% concordant with newborn screening follow-up data, even in challenging samples that contained a low fetal fraction (<5%) or at earlier gestational ages. Additionally, we obtained 98.5% concordance with newborn genotypes, including differentiating healthy fetal sickle cell carriers from homozygous healthy fetuses. The sensitivity of detecting fetal carrier status of beta hemoglobinopathies was 100% (90.8% to 100% CI), and the specificity was 96.4% (81.7% to 99.9 % CI). Conclusions: Single-gene NIPT is a highly accurate screen for prenatal detection of SCD and beta thalassemia. The results further suggest that the maternal carrier screen with reflex single-gene NIPT workflow can significantly improve the detection rates of at-risk pregnancies from <50% to >98%.

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Sickle Cell Disease

Cited by 306 publications

References 52 publications

Inpatient palliative care use by patients with sickle cell disease: a retrospective cross-sectional study

Inpatient palliative care use by patients with sickle cell disease: a retrospective cross-sectional study

Agonistic Anti-CD40 Antibody Triggers an Acute Liver Crisis With Systemic Inflammation in Humanized Sickle Cell Disease Mice

Clinical validity of single-gene non-invasive prenatal testing for sickle cell disease and beta thalassemia

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