Elliott Vichinsky

UCSF Benioff Children’s Hospital Oakland · hematolog oncology

Background: Acute chest syndrome (ACS) is the leading cause of mortality, accounting for 25% of all deaths among individuals with sickle cell disease (SCD). There is a lack of evidence-based laboratory and clinical risk stratification guidelines for diagnosing and managing ACS. Study Design and Methods: To better understand physician practices for...

Alpha‐thalassemia is an inherited blood disorder caused by impaired α‐globin chain production, leading to anemia and other complications. Hemoglobin H (HbH) disease is caused by a combination of mutations generally affecting the expression of three of four α‐globin alleles; disease severity is highly heterogeneous, largely driven by genotype. Notab...

Children and adults with sickle cell disease (SCD) have increases in morbidity and mortality with COVID-19 infections. The ASH Research Collaborative Sickle Cell Disease Research Network performed a prospective COVID-19 vaccine study to assess antibody responses and analyze whether mRNA vaccination precipitated any adverse effects unique to indivi...

Background Due to the risk of cerebral vascular injury, children and adolescents with high-risk sickle cell disease (SCD) experience neurocognitive decline over time. Haploidentical stem cell transplantation (HISCT) from human leukocyte antigen-matched sibling donors may slow or stop progression of neurocognitive changes. Objectives The study is t...

Introduction: Acute chest syndrome (ACS) is the leading cause of mortality, accounting for 25% of all deaths among individuals with sickle cell disease (SCD). The etiologies and clinical manifestations of ACS are variable, with a lack of clear risk stratification guidelines for the practicing clinician. Management of ACS is based on limited evidenc...

Introduction: Reproductive health education is lacking among individuals with sickle cell disease (SCD) despite many females reporting increased pain during menstruation. Research suggests that SCD-related pain associated with menstruation may be regulated with the use of hormonal therapy. Yet, education about safe and available contraceptive thera...

A multi-state, long term follow-up study of individuals with sickle cell disease (SCD) demonstrated an increase in mortality and morbidity in children and adults with COVID. mRNA vaccines are recommended for all SCD patients. Vaccination in individuals with SCD for other infections may be associated with impaired antibody responses. Concern has als...

Background Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evid...

Because women with transfusion-dependent thalassemia are seeking pregnancy, ensuring the best outcomes for both mother and baby require concerted and collaborative efforts between the hematologist, obstetrician, cardiologist, hepatologist, and genetic counselor among others. Proactive counseling, early fertility evaluation, optimal management of ir...

Clinical manifestations of α-thalassemia range from no symptoms to severe transfusion-dependent anemia. Alpha thalassemia trait is deletion of 1 to 2 α-globin genes, whereas α-thalassemia major (ATM; Barts hydrops fetalis) is the deletion all 4 α genes. All other genotypes of intermediate severity are categorized as HbH disease, a vastly heterogeno...

Intravascular hemolysis results in the release of cell-free hemoglobin and heme in plasma. In sickle cell disease, the fragility of the sickle red blood cell leads to chronic hemolysis, which can contribute to oxidative damage and activation of inflammatory pathways. The scavenger proteins haptoglobin and hemopexin provide pathways to remove hemogl...

The sickle cell mutation increases morbidity in those with sickle cell disease (SCD) and potentially sickle cell trait, impacting pulmonary, coagulation, renal, and other systems that are implicated in COVID-19 severity. There are no population-based registries for hemoglobinopathies, and they are not tracked in COVID-19 testing. We used COVID-19 t...

A prognostic scoring system that can differentiate β-thalassemia patients based on mortality risk is lacking. We analysed data from 3145 β-thalassemia patients followed through a retrospective cohort design for the outcome of death. An a priori list of prognostic variables was collected. β Coefficients from a multivariate cox regression model were...

Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine pa...

Objectives Thalassemic red blood cells (RBCs) have insufficient levels of adenosine triphosphate (ATP) to meet increased energy demands associated with globin chain precipitation and oxidative stress responses. Mitapivat is a first-in-class, small molecule, oral activator of pyruvate kinase (PK), a key glycolytic enzyme regulating ATP production. I...

Background Patients with non-transfusion-dependent thalassaemia (NTDT), although they do not require regular blood transfusions for survival, can still accrue a heavy burden of comorbidities. No approved disease-modifying therapies exist for these patients. We aimed to investigate the safety and efficacy of mitapivat (Agios Pharmaceuticals, Cambrid...

Objectives L-Glutamine was FDA-approved for sickle cell disease (SCD) in 2017, yet the mechanism(s)-of-action are poorly understood. This study investigates the potential activation of autophagy as a previously unexplored mechanism-of-benefit. Design Prospective, open-label, 8-week, phase-2 trial of oral L-glutamine (10 g TID) in patients with SCD...

Transition from pediatric to adult care for adolescents and young adults (AYA) with sickle cell disease (SCD) comes at a time when a range of biopsychosocial issues occur simultaneously. A new survey sought information from physicians who treat AYA with SCD about their practices in how they transition pediatric patients to adult care. An online sur...

Purpose Anterior pituitary iron overload and volume shrinkage is common in patients with transfusion-dependent anemia and associated with growth retardation and hypogonadotropic hypogonadism. We investigated the accuracy of different MRI-based pituitary volumetric approaches and the relationship between pituitary volume and MRI-R2, particularly wit...

In this work, we aimed to establish subgroups of clinical severity in a global cohort of β-thalassemia through unsupervised random forest (RF) clustering. We used a large global dataset of 7910 β-thalassemia patients and evaluated 19 indicators of phenotype severity (IPhS) to determine their contribution and relatedness in grouping β-thalassemia pa...

Objectives L-Glutamine is FDA-approved for sickle cell disease (SCD), yet the mechanism(s)-of-action are poorly understood. We performed a pharmacokinetics (pK) study to determine the metabolic fate of glutamine supplementation on plasma and erythrocyte amino acids in patients with SCD. Design A pK study was performed where patients with SCD fasti...

Objective Biomagnetic liver susceptometry (BLS) is a noninvasive method to quantify liver iron concentration (LIC). Here we report our findings from a prospective study which validates in vivo LIC from a SQUID biosusceptometer by in vitro LIC in fresh tissue and paraffin-embedded biopsies from patients at risk for iron overload. Materials and Metho...

Thalassaemia is caused by genetic globin defects leading to anaemia, transfusion‐dependence and comorbidities. Reduced survival and systemic organ disease affect transfusion‐dependent thalassaemia major and thalassaemia intermedia. Recent improvements in clinical management have reduced thalassaemia mortality. The therapeutic landscape of thalassae...

Background: The thalassemias are a group of red blood cell (RBC) disorders in which ineffective erythropoiesis and hemolysis occur due to imbalanced production and precipitation of globin chains. Thalassemic RBCs have insufficient levels of ATP to meet increased energy demands associated with globin chain imbalance, protein degradation, and cellula...

In β‐thalassaemia, the severity of inherited β‐globin gene mutations determines the severity of the clinical phenotype at presentation and subsequent transfusion requirements. However, data on associated long‐term outcomes remain limited. We analysed data from 2109 β‐thalassaemia patients with available genotypes in a global database. Genotype seve...

Objectives Thalassemias are characterized by ineffective erythropoiesis and hemolysis due to imbalanced production and precipitation of globin chains. Adenosine triphosphate (ATP) levels are reduced in thalassemic red blood cells (RBCs), despite increased energy demands to maintain RBC cell integrity. Mitapivat (AG-348) is an oral activator of RBC...

Children with sickle cell disease (SCD) are at high-risk of progressive, chronic pulmonary and cardiac dysfunction. In this prospective multicenter Phase II trial of myeloimmunoablative conditioning followed by haploidentical stem cell transplantation in children with high-risk SCD, 19 patients, 2.0–21.0 years of age, were enrolled with one or more...

Alleviating anaemia in patients with sickle cell disease (SCD) is crucial in managing acute complications, mitigating end‐organ damage and preventing early mortality. Some disease‐modifying and curative therapies have increased haemoglobin (Hb) levels to exceed 100 g/l, a threshold above which complications from red blood cell (RBC) transfusions ha...

Background: Sickle cell disease (SCD) is an inherited disorder in which pathology is driven by hemoglobin (Hb) polymerization and erythrocyte sickling, leading to chronic hemolytic anemia, and episodic vaso-occlusive crises (VOC). These manifestations of SCD contribute to the cumulative organ damage that leads to disability, reduced quality of life...

Background For decades, patients with sickle cell disease have had only a limited number of therapies available. In 2019, voxelotor (1500 mg), an oral once-daily sickle haemoglobin polymerisation inhibitor, was approved in the USA for the treatment of sickle cell disease in patients aged 12 years and older on the basis of HOPE trial data. To furthe...

Introduction: The clinical manifestations of sickle cell disease (SCD) result from an inherited mutation in the beta-globin chain of hemoglobin (Hb) that causes Hb tetramers to polymerize when deoxygenated. The resulting erythrocyte deformation causes mechanical obstruction of blood flow by sickled cells, hemolysis, anemia and end-organ injury. Whi...

The thalassaemia syndromes (TS) show different phenotype severity. Developing a reliable, practical and global tool to determine disease severity and tailor treatment would be of great value. Overall, 7910 patients were analysed with the aim of constructing a complication risk score (CoRS) to evaluate the probability of developing one or more compl...

Background Thalassemia Syndromes (TS) are commonly classified as transfusion-dependent-thalassemia (TDT) or non-transfusion-dependent thalassemia (NTDT) at diagnosis on the basis of requirement for lifelong regular transfusion therapy for survival. However, data from observational studies and expert opinion suggest that these categories may reflect...

Background: Sickle cell disease (SCD) is a lifelong, inherited disorder characterized by sickle hemoglobin (HbS) polymerization that results in red blood cell (RBC) sickling and results in complications such as hemolytic anemia, vaso-occlusive crises (VOCs), endothelial dysfunction, and organ damage. Large and rapid increases in hemoglobin (Hb) con...

Introduction: Heme, an iron-containing protoporphyrin, is an essential component of hemoglobin that binds oxygen for delivery to tissues. In sickle cell disease, intravascular hemolysis leads to the presence of cell-free hemoglobin and heme, which may contribute to oxidative damage and activation of inflammatory pathways. Hemoproteins such as hapto...

Background: Sickle cell disease (SCD) is a lifelong, inherited disorder characterized by mutations in the hemoglobin (Hb) subunit β gene that leads to the production of sickle hemoglobin (HbS). When HbS is deoxygenated, polymerization leads to red blood cell sickling and damage, resulting in hemolysis, chronic anemia, and episodic vaso-occlusive cr...

Introduction: In utero hematopoietic cell transplantation (IUHCT) has the potential to treat patients with blood disorders by taking advantage of bidirectional maternal-fetal tolerance during pregnancy. Although engraftment has only been seen in immunodeficient patients in the past, recent preclinical studies indicate that a higher dose of maternal...

Objective: Adolescents and adults with sickle cell disease (SCD) face pervasive disparities in health resources and outcomes. We explored barriers to and facilitators of care to identify opportunities to support implementation of evidence-based interventions aimed at improving care quality for patients with SCD. Methods: We engaged a representative...

The thalassemias are an inherited group of disorders caused by absent or abnormal globin chain synthesis and insufficient hemoglobin production resulting in moderate to severe anemia. Curative treatment with bone marrow transplant or gene therapy and more recent treatment advances are limited to a small number of patients. Thus, blood transfusion r...

Importance Sickle cell disease (SCD) is characterized by chronic pain and episodic acute pain caused by vasoocclusive crises, often requiring high doses of opioids for prolonged periods. In humanized mouse models of SCD, a synthetic cannabinoid has been found to attenuate both chronic and acute hyperalgesia. The effect of cannabis on chronic pain i...

Background Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan. Objective These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of th...

People with sickle cell disease (SCD) are reported to have low rates of HIV infection, slower progression to AIDS and lower HIV-associated mortality compared to the general population. Mechanisms of potential resistance to HIV in SCD are incompletely understood. We retrospectively reviewed the Transfusion Safety Study to compare HIV status between...

Background Patients with transfusion-dependent β-thalassemia (TDT) may experience transfusional iron overload and end-organ damage. While potentially curative, allogeneic hematopoietic stem cell (HSC) transplantation is limited by transplant-related risks and donor availability. Transplantation of autologous CD34+ cells encoding a βA-T87Q-globin ge...

BACKGROUND: Life expectancy for individuals with sickle cell disease (SCD) is shorter in California than in other states with multiple contributing factors. These include a shortage of adult hematologists expert in SCD management, lack of resources for the provision of comprehensive care, and limited options for disease modifying therapies. Adults...

Background: Sickle cell disease (SCD) is an inherited disorder in which pathology is driven by hemoglobin (Hb) polymerization and red blood cell sickling, leading to chronic hemolysis and anemia as well as episodic vaso-occlusion. These manifestations of SCD contribute to the cumulative organ damage that leads to disability and accelerated mortalit...

Background: Thalassemia is a group of inherited blood disorders in which genetic mutation(s) in the α- and/or β-globin locus lead to excess precipitation of β- or α-globin, respectively, and compromised red blood cell (RBC) survival. The condition is characterized by ineffective erythropoiesis and peripheral hemolysis, with resultant anemia. Adenos...

Introduction Thalassemia Syndromes (TS) are a group of inherited haemoglobin disorders characterized by different phenotype severity falling among heterozygote state, no transfusion dependent thalassemia (NTDT) and transfusion dependent Thalassemia (TDT) (Graffeo et al, 2018; Taher & Saliba, 2017). Several factors, independently by genotype and glo...

Background: Sickle cell disease (SCD) is an inherited disorder in which pathology is driven by hemoglobin (Hb) polymerization and red blood cell sickling, leading to chronic anemia and hemolysis as well as episodic vaso-occlusive crises (VOC). These manifestations of SCD contribute to the cumulative organ damage that leads to disability, reduced qu...

Established in 2002, the Iron Overload Program in Oakland relies on a biosusceptometer (Ferritometer®, model 5700, Tristan Technologies, San Diego, USA) utilizing low temperature SQUID technology to quantify liver iron concentration (LIC). The procedure is non-invasive and patients as young as 2 years can be been measured without sedation. The meas...

Background: Pulmonary complications of sickle cell disease (SCD) are diverse and encompass acute and chronic disease. The understanding of the natural history of pulmonary complications of SCD is limited, no specific therapies exist, and these complications are a primary cause of morbidity and mortality.Methods: We gathered a multidisciplinary grou...

Purpose: Sickle cell anemia is the most commonly inherited blood disorder in the United States. Despite its prevalence, clinicians know little about the extent of its impact on orofacial manifestations. Materials and methods: All patients with diagnoses of mandible fracture and sickle cell anemia admitted from 2004 through 2014 were identified u...

Background: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare genetic disorder characterised by progressive generalised dystonia and brain iron accumulation. We assessed whether the iron chelator deferiprone can reduce brain iron and slow disease progression. Methods: We did an 18-month, randomised, double-blind, placebo-controll...

Background Deoxygenated sickle hemoglobin (HbS) polymerization drives the pathophysiology of sickle cell disease. Therefore, direct inhibition of HbS polymerization has potential to favorably modify disease outcomes. Voxelotor is an HbS polymerization inhibitor. Methods In a multicenter, phase 3, double-blind, randomized, placebo-controlled trial,...

Impact statement: Therapy with vincristine (VCR), a vinca alkaloid, is widely used in many hematologic disorders and pediatric cancers, and acts by binding to the tubulin protein, to inhibit effective cell division. Our paper indicates that treatment of patients with a red cell disorder may require additional clinical interventions to compensate f...

Background While regular red blood cell (RBC) transfusions extend the lifespan of patients with transfusion‐dependent β‐thalassaemia (TDT), iron overload and end‐organ damage can result. The curative alternate, allogeneic haematopoietic stem cell (HSC) transplantation, is limited by donor availability and transplant‐related risks. LentiGlobin gene...

Background Sickle cell disease (SCD) is an inherited disorder caused by a single amino acid substitution in the β‐chain of hemoglobin (Hb) resulting in the production of sickle hemoglobin (HbS). When deoxygenated, HbS polymerizes, leading to red blood cell sickling and damage. This results in a triad of clinical features (anemia, hemolysis, and vas...

NATURE REVIEWS DISEASE PRIMERS The Primers in this collection will be free to download until 13th June 2019,https://www.nature.com/collections/tlmcpdxbph but once this time is up, you can use the free share URL, which is https://rdcu.be/bfUZh

Background SCD is a chronic debilitating disease secondary to frequent veno-occlusive events resulting in chronic organ damage, including cerebral vasculopathy, acute chest syndrome (ACS), pulmonary hypertension and a significantly shortened life-span (Bunn et al, NEJM, 1997; Lanzkron et al, PHR, 2013; Platt et al, NEJM, 1994). Importantly, SCD sur...

Background Advances in red blood cell (RBC) transfusion and chelation have improved the prognosis of patients with transfusion-dependent β-thalassemia (TDT); however, many patients experience organ damage due to iron overload and other complications. While potentially curative, allogeneic hematopoietic stem cell transplantation confers significant...

Background: Sickle cell disease (SCD) is a genetic disorder in which deoxygenation results in polymerization of mutated hemoglobin S (HbS) and triggers the downstream effects of red blood cell (RBC) deformation (sickling), hemolytic anemia, vaso-occlusion, inflammation, predisposition to infection, and chronic organ damage. Two distinct pathophysio...

BACKGROUND The severe forms of thalassemia are the most common inherited anemias managed with regular blood transfusion therapy. Transfusion policies and complications are critical to quality of life and survival, but there is a lack of standardized care. STUDY DESIGN AND METHODS A survey of 58 items was completed in 2016 by 11 centers in Californ...

Background Oxidative stress contributes to the complex pathophysiology of sickle cell disease. Oral therapy with pharmaceutical-grade l-glutamine (USAN, glutamine) has been shown to increase the proportion of the reduced form of nicotinamide adenine dinucleotides in sickle cell erythrocytes, which probably reduces oxidative stress and could result...

Background Donor availability and transplantation-related risks limit the broad use of allogeneic hematopoietic-cell transplantation in patients with transfusion-dependent β-thalassemia. After previously establishing that lentiviral transfer of a marked β-globin (βA-T87Q) gene could substitute for long-term red-cell transfusions in a patient with β...