Organizing national responses for rare blood disorders: the Italian experience with sickle cell disease in childhood

Alterations in the deformability of red blood cells (RBCs), occurring in hemolytic blood disorders such as sickle cell disease (SCD), contributes to vaso-occlusion and disease pathophysiology. However, there are few...

Download Full-text

Gene Replacement Therapy for Sickle Cell Disease and Other Blood Disorders

Hematology ◽

10.1182/asheducation-2008.1.193 ◽

2008 ◽

Vol 2008 (1) ◽

pp. 193-196 ◽

Cited By ~ 14

Author(s):

Tim M. Townes

Keyword(s):

Stem Cells ◽

Sickle Cell Disease ◽

Replacement Therapy ◽

Sickle Cell ◽

Lentiviral Vectors ◽

Gene Replacement ◽

Cell Disease ◽

Blood Disorders ◽

Gene Replacement Therapy ◽

Normal Human

Abstract Previous studies have demonstrated that sickle cell disease (SCD) can be corrected in mouse models by transduction of hematopoietic stem cells with lentiviral vectors containing anti-sickling globin genes followed by transplantation of these cells into syngeneic recipients. Although self-inactivating (SIN) lentiviral vectors with or without insulator elements should provide a safe and effective treatment in humans, some concerns about insertional mutagenesis persist. An ideal correction would involve replacement of the sickle globin gene (βS) with a normal copy of the gene (βA). We recently derived embryonic stem (ES) cells from a novel knockin mouse model of SCD and tested a protocol for correcting the sickle mutation by homologous recombination. Animals derived after gene replacement produced high levels of normal human hemoglobin (HbA), and the pathology associated with SCD was corrected. These experiments provided a foundation for similar studies in which our group collaborated with Rudolf Jaenisch’s laboratory to correct SCD by gene replacement in iPS (induced pluripotent stem) cells derived by direct reprogramming of sickle skin fibroblasts. Corrected iPS cells were differentiated into hematopoeitic progenitors that were transplanted into irradiated sickle recipients. The transplanted animals produced high levels of normal human HbA, and the pathology of SCD was corrected. These proof-of-principle studies provide a foundation for the development of gene replacement therapy for human patients with SCD and other blood disorders.

Download Full-text

Student screening for inherited blood disorders in Bahrain

Eastern Mediterranean Health Journal ◽

10.26719/2003.9.3.344 ◽

2021 ◽

Vol 9 (3) ◽

pp. 344-352

Author(s):

S. Al Arrayed ◽

N. Hafadh ◽

S. Amin ◽

H. Al Mukhareq ◽

H. Sanad

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

G6pd Deficiency ◽

High Performance ◽

Sickle Cell Trait ◽

Disease Incidence ◽

Cell Disease ◽

Blood Disorders ◽

Inherited Disorders ◽

Beta Thalassaemia

In Bahrain and neighbouring countries inherited disorders of haemoglobin, i. e. sickle-cell disease, thalassaemias and glucose-6-phosphate dehydrogenase [G6PD] deficiency, are common. As part of the National Student Screening Project to determine the prevalence of genetic blood disorders and raise awareness among young Bahrainis, we screened 11th-grade students from 38 schools [5685 students], organized lectures and distributed information about these disorders. Haemoglobin electrophoresis, high performance liquid chromatography, blood grouping and G6PD deficiency testing were performed. Prevalences were: 1.2% sickle-cell disease; 13.8% sickle-cell trait; 0.09% beta-thalassaemia; 2.9% beta-thalassaemia trait; 23.2% G6PD deficiency; 1.9% G6PD deficiency carrier. Health education, carrier screening and premarital counselling remain the best ways to reduce disease incidence with potentially significant financial savings and social and health benefits

Download Full-text

CRISPR cuts disease course short in blood disorders

Science Translational Medicine ◽

10.1126/scitranslmed.abg1756 ◽

2021 ◽

Vol 13 (575) ◽

pp. eabg1756

Author(s):

Bence György

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Gene Editing ◽

Disease Course ◽

Cell Disease ◽

Blood Disorders

Gene editing for sickle cell disease and β-thalassemia results in potential curative response.

Download Full-text

Current challenges in the management of patients with sickle cell disease – A report of the Italian experience

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-019-1099-0 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 5

Author(s):

Giovanna Russo ◽

Lucia De Franceschi ◽

Raffaella Colombatti ◽

Paolo Rigano ◽

Silverio Perrotta ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Cell Disease ◽

Italian Experience

Download Full-text

Challenges to management of pain in sickle cell disease

Thalassemia Reports ◽

10.4081/thal.2018.7482 ◽

2018 ◽

Vol 8 (1) ◽

Author(s):

Julie Kanter

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Patient Reported Outcomes ◽

Medical Providers ◽

Cell Disease ◽

Blood Disorders ◽

Pain Experience ◽

Multiple Dimensions ◽

Patient Reported ◽

Pharmacologic Agents

Sickle Cell Disease (SCD) is one of the most common blood disorders in the world. Pain is the primary reason for which individuals with SCD interact with the healthcare system. Generally speaking, there are two types of SCD pain: vaso-occlusive pain (or sickle cell disease crisis) and chronic pain caused by an accumulation of organ and tissue damage over time. However, despite its frequency, we have limited understanding about what causes pain in sickle cell disease, how best to manage pain in SCD and (most importantly) how to prevent pain in SCD. For medical providers, pain is also an elusive target due to the difficulty in objectively measuring pain and the importance of relying on patient reported outcomes. To face the challenges in managing pain in SCD, we will review the current understanding of the pathophysiology of vaso-occlusion, the multiple dimensions of the pain experience, and the current methods of measuring and managing pain. We will also review new pharmacologic agents undergoing clinical trials in SCD that will help to prevent pain and improve outcomes in SCD.

Download Full-text

Baby on board: what you need to know about pregnancy in the hemoglobinopathies

Hematology ◽

10.1182/asheducation.v2012.1.208.3798270 ◽

2012 ◽

Vol 2012 (1) ◽

pp. 208-214 ◽

Cited By ~ 21

Author(s):

Rakhi P. Naik ◽

Sophie Lanzkron

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Early Recognition ◽

Optimal Management ◽

Cell Disease ◽

Blood Disorders ◽

Successful Pregnancy ◽

Unique Challenge ◽

Gestational Period ◽

Fetal Complications

Abstract Pregnancy poses a unique challenge to patients with sickle cell disease and β-thalassemia, who often have exacerbations of hemolysis or anemia during the gestational period, experience higher rates of obstetric and fetal complications, and may have distinct underlying comorbidities related to vasculopathy and iron overload that can endanger maternal health. Optimal management of pregnant women with hemoglobinopathies requires both an understanding of the physiologic demands of pregnancy and the pathophysiology of disease-specific complications of inherited blood disorders. A multidisciplinary team of expert hematologists and high-risk obstetricians is therefore essential to ensuring appropriate antenatal maternal screening, adequate fetal surveillance, and early recognition of complications. Fortunately, with integrated and targeted care, most women with sickle cell disease and β-thalassemia can achieve successful pregnancy outcomes.

Download Full-text

Individualized identification of disturbed pathways in sickle cell disease

Open Life Sciences ◽

10.1515/biol-2017-0049 ◽

2017 ◽

Vol 12 (1) ◽

pp. 418-424

Author(s):

Chun-Juan Lu ◽

Yan Wang ◽

Ya-Li Huang ◽

Xin-Hua Li

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Differentially Expressed Gene ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Cell Disease ◽

Blood Disorders ◽

Pathway Data ◽

Level Statistics ◽

Gene Level

AbstractBackgroundSickle cell disease (SCD) is one of the most common genetic blood disorders. Identifying pathway aberrance in an individual SCD contributes to the understanding of disease pathogenesis and the promotion of personalized therapy. Here we proposed an individualized pathway aberrance method to identify the disturbed pathways in SCD.MethodsBased on the transcriptome data and pathway data, an individualized pathway aberrance method was implemented to identify the altered pathways in SCD, which contained four steps: data preprocessing, gene-level statistics, pathway-level statistics, and significant analysis. The changed percentage of altered pathways in SCD individuals was calculated, and a differentially expressed gene (DEG)-based pathway enrichment analysis was performed to validate the results.ResultsWe identified 618 disturbed pathways between normal and SCD conditions. Among them, 6 pathways were altered in > 80% SCD individuals. Meanwhile, forty-six DEGs were identified between normal and SCD conditions, and were enriched in heme biosynthesis. Relative to DEG-based pathway analysis, the new method presented richer results and more extensive application.ConclusionThis study predicted several disturbed pathways via detecting pathway aberrance on a personalized basis. The results might provide new sights into the pathogenesis of SCD and facilitate the application of custom treatment for SCD.

Download Full-text

Healthy People 2020 Blood Disorders and Blood Safety: A Vision of Improved Health for Patients with Sickle Cell Disease, Thalassemias and Hemophilia

Blood ◽

10.1182/blood.v118.21.4771.4771 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4771-4771

Author(s):

Ellen M. Werner ◽

Lorraine Brown ◽

Kathryn L. Hassell ◽

Donna DiMichele

Keyword(s):

Public Health ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Healthy People ◽

Blood Safety ◽

Cell Disease ◽

Blood Disorders ◽

Governmental Agencies ◽

Healthy People 2020 ◽

Health Objectives

Abstract Abstract 4771 In December 2010, the US Department of Health and Human Services released Healthy People 2020 (HP2020) Objectives for the nation. For the first time in its thirty-year history, US health objectives include rare blood disorders and blood safety (BDBS). HP2020 is a public health program that incorporates current clinical evidence and best practices in medicine and public health to identify public health priorities. The objectives are not clinical practice guidelines. Rather, they are scientifically-based, quantified goals to improve the health of specific populations, such as children and older adults. Their development and implementation necessitate partnerships among governmental agencies, organizations, private companies, and medical and health associations at the local, state and national levels. Partners collaborate on implementing activities to reach targeted health objectives for specific populations using educational campaigns, media and other communication venues. NHLBI led the effort with HRSA, CDC, FDA, and the Office of the Secretary to develop, vet and plan implementation of the BDBS objectives. The development process was based on qualitative research methods such as key informant interviews, semi-structured interviews and categorization of data into patterns. For example, categorization of interview results (“data”) identified specific objective topics, such as screening for complications and penicillin prophylaxis in sickle cell patients aged 4 months to 5 years. Other BDBS Objective topics are: vaccinations; patient and family referrals; care in a medical home; disease-modifying therapies; avoidable hospitalizations; high school completion; community health education; awareness of carrier status; joint health; and alloimmunization in chronic transfusion. http://healthypeople.gov/2020/topicsobjectives2020/default.aspx By sponsoring the BDBS objectives, lead governmental agencies commit to collecting, analyzing and reporting data on progress. We adopted the default target of a 10% improvement for each objective by 2020. If targets for each objective are met, the question will be: What is the impact of reaching these targets on morbidity, mortality and quality of life for patients with sickle cell disease, thalassemias and hemophilia? Disclosures: Hassell: NIH: Research Funding.

Download Full-text